Decision 166/QD-BYT 2024 criteria for evaluating ASEAN Common Submission Dossier Template of non-in-vitro diagnostic medical devices

THE MINISTRY OF HEALTH
^______

THE SOCIALIST REPUBLIC OF VIETNAM
Independence - Freedom - Happiness
^{______________________}

No. 166/QD-BYT

Hanoi, January 22, 2024

FOR THE MINISTER
THE DEPUTY MINISTER



Do Xuan Tuyen

NO.

HEADING

REQUIRED CONTENTS

INSTRUCTIONS FOR ASSESSMENT

DOCUMENTATION

1

Synopsis of general description of medical devices

1.1

Brief, general description of medical devices

Required information:

- Description of introduction to the medical devices.

- Intended use/ indications for use.

- New features, if any (for example: use of nanotechnology, artificial intelligence, etc.).

- Description of introduction to the medical devices includes:

+ Name

+ Category/code of product (based on CFS)

+ Global Medical Device Nomenclature - GMDN (if any)

+ Software, software version (if any)

+ Name and unique registration number (if any)

- New features, if any (for example: use of nanotechnology, artificial intelligence, etc.).

- Documentation of general description of medical devices.

- Instructions for use or technical documents issued by the product owner.

- Attached documents such as: links, data sheets, instructions for use, etc.

1.2

History of product circulation on the market

List of countries in which the product was sold on the market (if any).

Provide a list of countries in which the product was sold on the market, attached to the first year (if any) in which the product was sold on such market.

Attached documents such as: Certificate of Free Sale (CFS), link to number of marketing authorization, etc. (if any)

1.3

Intended use, indications for use

Intended use and/or indications for use of the medical devices.

If the intended use and/or indications for use of the medical devices are similar to those on the label or instructions for use of such medical devices.

Labels, user manuals, etc.

1.4

Information on the grant of marketing authorization in countries

Information on marketing authorization of the products in the following countries: EU countries, Japan, Canada, Australia (TGA), USA (FDA), UK, Switzerland, Korea, China.

Information on marketing authorization of the products in the following countries: EU countries, Japan, Canada, Australia (TGA), USA (FDA), UK, Switzerland, Korea, China, etc. including licensing status (approved, pending approval, rejected, non-registration, etc.), intended use, indications for use, date of first grant. For products granted a certificate of marketing authorization in EU countries, the latest grant date may be written if the first grant date is not stated. This information can be presented in a tabular format as given below:

Attached documents: guidelines or documents proving information on the marketing authorization or the provision of copies or links to online documents on the grant of marketing authorization in the above-mentioned countries (if any)

1.5

Important information regarding the safety and efficiency of medical devices

Provide documents signed and granted within the last 5 years, including:

- Adverse events, number of adverse events or frequency of occurrence (total number of adverse events recorded per total number of products sold).

- Corrective actions to ensure safety in the market. If there have been no adverse events, no corrective action since selling products or over the latest 5 years, a written confirmation from the products’ owner shall be submitted.

Provide brief information on adverse incidents that have occurred and corrective actions to ensure safety in the market since the product was introduced to the market or over the latest 5 years.

Brief information on adverse events that have occurred, containing at least a description of the adverse events, number of adverse events or frequency of occurrence (total number of adverse events recorded per total number of products sold). This information can be presented in a tabular format as given below:

Information on corrective actions to ensure the safety in the market, containing at least date of occurrence, brief description of the event, and name of the country or territory that took corrective action. This information can be presented in a tabular format as given below:

If there have been no adverse events, no corrective action since selling products or over the latest 5 years, a written confirmation from the products’ owner shall be submitted.

Indicate whether the medical device contains one of the following ingredients:

- Human or animal cells, tissues or their derivatives intended for use in a non-viable form, for example artificial heart valves originating from pigs, cat intestines, etc.

- Are the cells, tissues or derivatives of microbial or recombinant origin? For example, skin plumping products based on hyaluronic acid obtained from bacterial fermentation process, etc.

- Contain radioactive or ionizing ingredients (e.g. X-ray); or non-ionizing ingredients (e.g. laser, ultrasound, etc.).

Documents declaring adverse events, number of adverse events or frequency of occurrence, corrective actions or written confirmation of the products’ owner (consular legalization is not required). Documents can be written in English or Vietnamese

2

Table of conformity to essential rules: in accordance with Appendix II

(If the medical device has been granted a marketing authorization in EU countries, a table of conformity to essential rules may be submitted according to EU regulations).

3

Prescription of the medical device

3.1

Description and presentation of characteristics of the medical devices

- Detailed description of the characteristics of the medical device.

- Description of components and accessories used to help the device operate as well as package.

- Full description of each functional component, material or raw material of the medical device, accompanied by a visual of the medical device in the form of a diagram, photograph or drawing, as appropriate.

- Detailed description of characteristics of the medical device for explaining principles of action of the medical device, explaining basic science concepts that make up the fundamentals of the medical device.

- Description of components and accessories used to help the device operate as well as package including: configuration, design features of components.

- Full description of each functional component, material or raw material of the medical device, accompanied by a visual of the medical device in the form of a diagram, photograph or drawing, as appropriate.

Detailed description of the medical device.

Technical documents issued by the owner.

3.2

Instructions for use

Provide instructions for use from the product owner

All necessary information provided from the product owner including the summary procedures, methods, frequency, timing, quantities and preparations that must be followed for the safe use of the medical device.

Detailed description of the medical device (if any) or original instructions for use issued by the owner of the medical device (enclosed with a Vietnamese translation).

Technical documents issued by the owner.

3.3

Contraindications

In case the medical device cannot be used for patient safety reasons, it must be in accordance with the contents written on the label or Instructions for use of the medical device.

Diseases or cases and patient groups for which medical devices should not be used for the purpose of diagnosis, treatment or mitigation of disease.

Information on cases where the medical device cannot be used for patient safety reasons, for example: due to the patient's medical history, physiological characteristics, etc. in accordance with the content written on the label or instructions for use of the medical device.

General description of diseases or cases and patient groups for which medical devices should not be used for the purpose of diagnosis, treatment or mitigation of disease. Contraindications that are cases for which medical devices should not be used because the risks clearly outweigh the potential benefits.

Detailed description of the medical device (if any) or original instructions for use issued by the owner of the medical device.

Contraindications (if any).

Technical documents issued by the owner.

3.4

Warning

Warning on specific dangers that users need to know before using medical devices.

Warning information on specific dangers that users need to know before using medical devices, including preventive measures to protect patients from risks caused by the use of such medical devices.

Detailed description of the medical device (if any) or original instructions for use issued by the owner of the medical device.

3.5

Cautions

Warn the user to take necessary precautions for the safe and effective use of the medical device.

Warn the user to take necessary precautions for the safe and effective use of the medical device. May include actions to be taken to avoid effects to the patient/user, which may not be life-threatening or cause serious injury, but of which the user should be aware. Cautions may also warn the user of the adverse effects of using the medical device or of misuse of the medical device and of the precautions required to avoid such effects.

Detailed description of the medical device (if any) or original instructions for use issued by the owner of the medical device.

Technical documents issued by the owner.

3.6

Potential adverse effects

Possible unintended and serious consequences for the patient/user, or side effects from using the medical device under normal conditions

These are unintended and serious consequences (death, injury, or serious adverse events) that may occur to the patient/user, or side effects from the use of the medical device under normal conditions, which are recorded through clinical testing and after-sales monitoring.

Detailed description of the medical device (if any) or original instructions for use issued by the owner of the medical device.

Potential adverse effects (if any).

Technical documents issued by the owner.

3.7

Alternative therapy

Alternative procedures or actions for diagnosing, treating or mitigating the disease or condition for which the medical device is intended.

Assess the description of alternative procedures or actions for diagnosing, treating or mitigating the disease or condition for which the medical device is intended.

Detailed description of the medical device (if any).

Alternative therapy (if any).

3.8

Materials

Description of materials of the medical device and its characteristics for proving the conformity with relevant essential rules.

Assess the description of materials of the medical device and its characteristics for proving the conformity with relevant essential rules.

For non-in-vitro diagnostic medical devices:

- Provide a list of materials of the medical device that come into direct contact with the body (e.g.  mucous membrane) and indirect contact with the body (e.g. circulation of extracellular fluid (ECF)), and their chemical, biological and physical characteristics.

- For medical devices emitting ionizing radiation, information on the source of radiation (e.g.: radioactive isotopes) and materials used to protect users and patients from unwanted emissions must be provided.

- In case there are special requirements regarding the safety of raw materials such as impurities, levels of residue and exposure to plasticizers such as Bis (2- ethylhexyl) phthalate (DEHP), it is necessary to provide additional certificates of compliance to relevant standards, testing certificates, or safety risk assessment of such material. Depending on the risk of exposure to these materials, additional measures may be required, such as notifying the user of the presence of these materials by labeling the product.

Standards or testing certificates or declarations of conformity to the recognized standards applied by the product owner

3.9

Other relevant specifications

Functions and specifications of medical devices for proving the conformity with relevant essential rules.

Functions and specifications of medical devices including accuracy, sensitivity, specificity of medical measuring and diagnostic devices, reliability and other factors (if relevant); and other specifications including chemistry, physics, electricity, mechanics, biology, software, sterility, stability, storage, transportation and packaging for proving the conformity with relevant essential rules.

Reports or declarations of conformity to the recognized standards applied by the product owner.

Other relevant specifications (if any)

3.10

Other information

Other important characteristics that are not mentioned above for proving the conformity with relevant essential rules.

Other important characteristics that are not mentioned above for proving the conformity with relevant essential rules (e.g. biocompatibility of medical devices, etc.).

Note: In case the aforementioned information is stated in the instructions for use, the instructions for use may be used for reference.

4

Synopsis of design verification and validation

(This section should summarize or reference or contain design verification data and design validation data, appropriate to the complexity and risk classification of the medical device.”

4.1

Preclinical studies

- Information on biocompatibility tests performed on materials used in the medical device.

- Physical preclinical testing data, as appropriate.

- Reports on preclinical studies on animals used to demonstrate possible effects of the medical device on humans.

- Evidences of electrical safety and electromagnetic compatibility.

- Sterilization validation reports for sterilized medical devices.

- Evidences of cybersecurity for network-connected, internet-connected or wireless medical devices.

- Provide detailed information on all biocompatibility tests performed on materials used in the medical device. All significantly different materials must be described. Description of tests, results and data analyses must be provided.

- Provide complete physical pre-clinical testing data, as appropriate. The report must include the product owner's objectives, methods, results, and conclusions for all physical studies of the medical device and components. Physical testing shall be performed to predict the adequate response of the medical device to physical stress, adverse conditions and effects, long-term use and all known and possible inoperability errors.

- Provide reports on preclinical studies on animals used to demonstrate possible effects of the medical device on humans. These studies must be performed in compliance with good laboratory practice. The report must include the product owner's objectives, methods, results, analysis, and conclusions. The conclusion of the study must address the interactions of the medical device with animal fluids and tissues and the functional effectiveness of the medical device in experimental animal model(s). The rationale (and limitations) of choosing specific animal models should be discussed.

- Provide evidences of electrical safety and electromagnetic compatibility. For example, if the owner declares that the product meets the requirements of IEC 60601-1 and IEC 60601-1-2, the summary test report and/or certificate of conformity must be provided to demonstrate that the medical device meets these standards.

- For sterilized medical devices, sterilization validation reports must be provided. If the sterilant is toxic or produces toxic residues (e.g.: Ethylene Oxide), data and test methods must be provided to demonstrate that the amount of sterilant or residue is within acceptable limits.

- Provide evidences of cybersecurity for network-connected, internet-connected or wireless medical devices. Such as: analyses of risks and possibilities of cyber attacks, cyber security control methods, plans, processes or mechanisms for monitoring, promptly detecting and managing security-related threats during the life cycle of the medical device. Declarations from the manufacturer or the owner stating that the medical device has equipped with network connection, internet connection or wireless connection to ensure cyber security and safety may be provided.

Documents proving the compliance with product characteristics, for example:

- Biocompatibility test reports or detailed information on test reports on all biocompatibility tests performed on blood-contacting materials used in the medical device. All significantly different materials must be described. Description of tests, results and data analyses must be provided.

- Physical preclinical testing data.

- Reports on preclinical studies on animals.

- Electrical safety certificates.

- Sterilization validation report.

- Cyber ​​security certificate or declaration from the manufacturer or the owner of medical devices with network connection, internet connection or wireless connection ensuring cyber security safety or cyber security risk assessment report.

- Preclinical studies (if not mentioned in the Clinical Report).

4.1.1

Software verification and validation studies

List of information about software and its versions.

The correctness of a software product is another important product characteristic that cannot be fully validated in a finished product. The product owner shall list information on software and its versions (up to the date of submission of the application). This information includes results of the verification, validation and testing of the software done internally and in user’s environments prior to official launch, for all different hardware configurations such as mentioned on the label or in the instructions for use of the product, as well as representative data obtained from both test environments

List of information about software and its versions.

4.1.2

Medical devices containing biological materials

Provide research results demonstrating that remedial measures related to the risks from infectious agents have been adequately implemented.

Must provide research results demonstrating that remedial measures related to the risks from infectious agents have been adequately implemented. This section will include virus removal results with known threats. Donor screening concerns must be fully addressed and methods of obtaining human material should be fully described. Process validation results are required to demonstrate that manufacturing processes have been applied to minimize biological risks.

- Research results demonstrating that remedial measures related to the risks from infectious agents have been adequately implemented.

- Animal tissue risk assessment or similar document.

4.2

Clinical evidence

Provide a clinical evaluation report of the medical device.

Provide a clinical evaluation report of the medical device. This evaluation report may be in the form of a systematic review of available references, be based on clinical experience with that medical device or similar medical device, or may be by clinical studies. Clinical studies are often necessary for high-risk medical devices, or medical devices with little or no clinical experience.

The clinical evaluation report includes purposes and context of the clinical evaluation, input clinical data, data appraisal and analysis, conclusions about safety and effectiveness of the medical device.

The clinical evaluation report should have all the necessary information as an independent document for consideration by regulatory agencies. The clinical evaluation report should provide an overview of:

- Technology used by such medical device, indications for use, statements about the safety and clinical effectiveness of such medical device, if any.

- Nature, scope and scale of the assessed clinical data.

- Clinical data and recognized standards proving the safety and effectiveness of medical device.

“A clinical investigation report of the medical device” shall be provided, including clinical data, clinical evaluation, clinical evidence, clinical efficiency, etc.

4.2.1

Data collected from existing references

Clinical evidences of the performance shall be provided and medical device-related studies conducted in Vietnam or other countries may be included.

In case the product owner uses existing studies and references to prove the safety and performance of the medical device, copies of these documents should be provided.

Clinical evidences of the performance may include medical device-related studies conducted in Vietnam or other countries. These evidences may be collected from related studies published in international medical journals. Documentation of clinical evidence must include objectives, methods and results, presented in clear and meaningful context. Before reaching conclusions of results of clinical studies, discussions in context with published documents are required.

List of existing studies and references used to prove the safety and performance of the medical device or clinical reports or clinical evaluation reports (CER).

4.2.2

Data from clinical experience

The data on the clinical experience of the same or similar product shall be provided.

Clinical experience is clinical data obtained from clinical use of the product, not from clinical studies. Clinical experience can be clinical experience of such product itself or a similar product.

Clinical experience can be obtained from the following data:

- After-sales monitoring reports of owners, regulatory authorities, systematic studies (may contain unpublished long-term research data on safety and performance).

- Data on adverse events that have occurred, obtained from product owners or regulatory agencies.

- Data obtained from patients using such medical device in the pre-market marketing aid program.

- Information on clinically relevant corrective actions such as recalls, notifications, hazard warnings.

After-sales data reports.

4.2.3

Data from clinical investigation

Clinical investigation data shall be provided for the purpose of assessment of safety and performance of the medical device.

The clinical investigation is a systematic investigation or study on or in human subjects, undertaken to assess the safety and performance of the medical device.

The clinical investigation may be undertaken by the medical device’s owner or by a third party on behalf of the owner. The clinical investigation should be designed, conducted and reported in conformity with ISO 14155 standards, Part 1 and 2, Clinical Investigations of Medical Devices for Human Subjects, or in conformity with an equivalent standard, and in compliance with regulations of the host country.

The clinical investigation must conform to the ethical standards of the Declaration of Helsinki.

Study design (study protocol) and reports on study results according to ISO 14155 (Parts 1 and 2, Clinical Investigations of Medical Devices for Human Subjects), or equivalent standards, or standards in host countries or clinical investigation reports or equivalent documents.

5

Labels of medical devices

5.1

Label samples on medical devices and packaging

Label samples must meet the requirements in accordance with Decree No. 43/2017/ND-CP and Decree No. 111/2021/ND-CP.

Label samples must be presented in print, text or images, provided or attached to one or more layers of packaging, including outer packaging and direct packaging. If it is impossible to provide physical label samples (e.g. a large warning label attached to an X-ray machine), the information may be provided in an alternative form, such as an image or technical drawing.

Label samples must meet the requirements in accordance with Decree No. 43/2017/ND-CP and Decree No. 111/2021/ND-CP as follows:

- Name of the medical device: consistent with the medical device applied to grant a number of marketing authorization.

- Name and address of the holder of marketing authorization number: consistent with the declared content.

- Number of marketing authorization of the medical device.

- Origin of the medical device, in case of unknown origin, the place where the finishing process of the medical device took place shall be written.

- Name and address of medical device’s owner: consistent with the declared content.

- Date of manufacture, expiry date: for sterilized or disposable medical devices, reagents, calibration substances, control materials, chemicals, the expiry date must be written. In other cases, the date of manufacture or expiry date shall be written; if the medical device is a machine/equipment, the year of manufacture or month, year of manufacture shall be written.

- Batch number or serial number of the medical device.

- Information on warning, instructions for use, storage instructions, warranty conditions: can be shown directly on the medical device label or the instructions for looking up this information on the medical device label are clearly stated.

- Instructions for looking up information on: warranty conditions, instructions for use of the medical device.

For imported medical devices, the label sample must include both the original label and the Vietnamese secondary label (if any). The label sample must include all products stated in the application for marketing authorization. In case the application is submitted according to the medical device family or a system of multiple comparable medical devices, a label sample as a representative sample with a note of differences between label samples of the medical device shall be submitted.

Original product label (for imported equipment).

Vietnamese product label design.

5.2

Instructions for use in Vietnamese

Instructions for the physician or end user to use the medical device safely and for its intended use.

Include instructions for the physician or end user to use the medical device safely and for its intended use. Instructions for use should include information on indications, contraindications, warnings or precautions, potential adverse effects, alternative therapies, and conditions of storage and use to maintain safety and performance of the medical device.

Instructions for use of the medical device

6

Risk analysis

Results of risk analysis

List of possible risks for the medical device. Present the assessment of these risks for comparison of them with the declared benefits of the medical device and methods used to reduce risks to an acceptable level.

Provide a list of possible risks for the medical device. Indirect risks from the medical device may originate from hazards caused by the medical device, such as moving parts causing long-term injuries, or from harms to the user, such as ionizing radiation from an X-ray machine. Assessments of these risks for comparison of them with the declared benefits of the medical device and methods used to reduce risks to an acceptable level must be presented. The individuals or organizations performing the risk analysis must be clearly identified. The techniques used to analyze risks must be defined to ensure the appropriateness to the medical device and the risks involved.

List of risk analyses or risk analysis reports and other documents such as: risk analysis plans, risk analysis methods, risk analysis results (if any)

7

Manufacture information

7.1

Information on the manufacturer

Name and address of the manufacturing establishments and sterilization establishments.

List the names and addresses of the manufacturing establishments and sterilization establishments of all manufacturers participating in the processes of manufacture and sterilization (including third-party manufacturers and sterilizers).

List of names and addresses of manufacturing establishments and sterilization establishments (presented on the license for marketing authorization).

7.2

Manufacturing process

Overview of the manufacturing process.

Include information serving the general perception of the manufacturing process. No proprietary details are required. This information can be presented in the form of a manufacturing flow diagram that briefly describes the manufacturing process, in-process quality control, assembly, quality control and packaging of the final product.

If multiple manufacturers are involved in the manufacturing process to complete a product, it is necessary to clearly state which activities each manufacturer is involved in.

A general description of the manufacturing process or manufacturing diagram.

No.

HEADING

REQUIRED CONTENTS

INSTRUCTIONS FOR ASSESSMENT

DOCUMENTATION

General requirements

1

Medical devices must be designed and manufactured so that when they are used under conditions and for the intended purposes, and with the knowledge and experience of users, they will not cause damage to health or safety of patients, users or others, provided that any risks associated with the use of these medical devices for their intended purposes are acceptable risks when considering benefits for patients and in accordance with requirements for health and safety protection at a high level.

Write “Yes", if such essential rules are applicable to the medical devices;

Write “No", if such essential rules are not applicable to the medical devices.

If one essential rule is not applicable to the medical devices, explanations are required. For example, if a medical device does not contain biological materials, in the column “applicable requirements”, write "No" and specify that the medical device does not contain biological materials.

Technical documents proving the product meets essential rules, e.g. certificates, study reports, test results:

- ISO 13485

- ISO 14971

- EN ISO 18113-1

- IEC 61326-1

- IEC 61326-2-6

- IEC 60601-1

Note: Accepting reports different from the Schedule in the Appendix - Table of conformity to essential rules of Decision No. 2426/QD-BYT.

2

The solutions of the medical device’s owner for the design and manufacture of medical device must be in accordance with safety principles, taking into account the level of scientific and technical development. In the process of choosing the appropriate solution for the design and manufacture of medical devices, to minimize the risks associated with the use of medical devices, the product owner must follow the following principles:

• identify hazards and associated risks arising from the use of the medical devices and the foreseeable misuse,

• eliminate or minimize risks reasonably through safe design and manufacturing,

• for risks that cannot be eliminated, adequately implement protective measures, including warnings if necessary, and

• inform users of residual risks.

3

The medical device must achieve the performance intended by the medical devices’ owners and be designed, manufactured, and packaged in such a way that, during intended conditions of use, they are suitable for their intended purpose(s).

4

The technical characteristics mentioned in Clauses 1, 2 and 3 do not cause adverse effects to such a degree that the health or safety of patients or users and other persons is compromised throughout the expected life of the medical devices, when the medical devices are subjected to the stresses which can occur during normal conditions of use and have been maintained and calibrated according to the instructions of medical devices’ owners.

5

Medical devices must be designed, manufactured and packaged in a way that ensures their technical characteristics, when used for their intended purposes, are not adversely affected during transport and storage if the transportation and storage are carried out in accordance with the instructions and information provided by the medical devices' owners

6

The benefits must outweigh any unwanted side effects to the intended effect.

7

Medical devices require clinical evidence, appropriate for their use and risk classification, demonstrating that the devices comply with the respective essential principles.  The clinical evaluation procedures must be applied.

Requirements for design and manufacturing

8

Chemical, physical and biological properties

8.1

Medical devices must be designed and manufactured in a way that ensures requirements for technical characteristics mentioned in Clauses 1 to 6 of “General requirements” are satisfied. Particular attention should be paid to:

• selection of materials to be used, in particular regarding toxicity, flammability,

• physical and chemical properties of the materials to be used,

• compatibility between the materials to be used and biological tissues, cells, body fluids, and specimens, taking into account the intended use of the medical device,

• selection of materials to be used must reflect issues such as abrasion, hardness and resistance of metal.

8.2

Medical devices must be designed, manufactured and packaged in a way that reduces risks caused by pollutants and residues for patients and relevant persons during transport, storage and use of the medical devices. For minimizing risks, it is necessary to pay special attention to duration and frequency of tissue contact during transport, storage and use of the medical devices.

8.3

Medical devices must be designed and manufactured in a way that they can be safely used with the materials, substances and gases to which they are exposed during normal conditions of use or in routine procedures; if medical devices are used to deliver drugs, they must be designed and manufactured in a way that they are compatible with the medicinal products concerned and the action of such drugs is maintained for their intended use.

8.4

If a medical device contains a substance that, if it is used separately, could be considered a medicinal product under the relevant legislation and has the effect of supporting the action of the medical device on the body, the safety, quality and performance of the medical device as well as the safety, quality and effectiveness of the combined medicinal product must be verified. The “medicinal product" referred to herein includes stable derivatives from human blood or plasma.

8.5

Medical devices must be designed and manufactured in a way that minimizes risks caused by substances that may seep or leak from the medical device.

8.6

Medical devices must be designed and manufactured in a way that minimizes risks posed by inadvertent ingress or release of substances from the medical devices, taking into account the nature of the environment in which they are intended to be used.

9

Infection and microbial contamination

9.1

Medical devices and manufacturing processes must be designed in a way that eliminates or minimizes, reasonably and appropriately, risks of infection to any person. The design must:

• allow for easy handling, and, if necessary:

• appropriately minimize any microbial leakage and/or microbial exposure during use;

• minimize the contamination from the patient, user or other person to the medical device or specimen and vice versa during use.

9.2

In case a medical device is composed of substances of biological origin, the risk of infection must be minimized to the maximum reasonable and appropriate degree by selecting appropriate sources, sample donors and substances, and using validated inactivation, conservation, testing and control procedures, as appropriate. This requirement may not be applicable to certain in vitro diagnostic medical devices if viral activity and infectious agents are essential to the intended use of the devices or if being removed or inactivated, the performance of such in vitro diagnostic medical devices will be affected.

9.3

Products made from non-living tissues, cells and substances of animal origin that are determined to be medical devices will be considered to have ingredients of animal origin under relevant regulations, be subject to veterinary control and supervision for the intended use of these tissues. The medical devices' owners should maintain information about the geographical origin of animals. The processing, storage, inspection and handling of tissues, cells and substances of animal origin must be carried out in a manner that ensures optimal safety. In particular, the safety related to viruses and other infectious agents must be achieved by validated methods of removal or inactivation during the manufacturing process. This requirement may not be applicable to certain in vitro diagnostic medical devices if other viral activity and infectious agents are essential to the intended use of the products or if being removed or inactivated, the performance of such in vitro diagnostic medical devices will be affected.

9.4

For products made from cells, tissues and derivatives of bacterial or recombinant origin that are determined to be medical devices, the selection of sample sources/donors, processing, preservation, testing and handling of cells, tissues and derivatives of such origin must be carried out in a manner that achieves optimal safety. In particular, the safety related to viruses and other infectious agents must be achieved by validated methods of removal or inactivation during the manufacturing process. This requirement may not be applicable to certain in vitro diagnostic medical devices if other viral activity and infectious agents are essential to the intended use of the products or if being removed or inactivated, the performance of such in vitro diagnostic medical devices will be affected.

9.5

For products composed of non-living tissues, cells, and substances of human origin that are determined to be in vitro diagnostic medical devices, the selection of sample sources, sample donors, and/or substances of human origin, the processing, storage, testing and handling of tissues, cells and substances of such origin must be carried out in a manner that ensures optimal safety. In particular, the safety related to viruses and other infectious agents must be achieved by validated methods of removal or inactivation during the manufacturing process. This requirement may not be applicable to certain in vitro diagnostic medical devices if other viral activity and infectious agents are essential to the intended use of the products or if being removed or inactivated, the performance of such in vitro diagnostic medical devices will be affected.

9.6

Medical devices labeled as having a specific microbial state must be designed, manufactured and packaged to ensure that they remain in that state when placed on the market and remain so under the transport and storage conditions specified by the medical devices’ owners.

9.7

Medical devices labeled as sterile must be designed, manufactured and packaged to ensure that the product remains sterile when placed on the market and remain so under the transport and storage conditions specified by the medical devices’ owners.

9.8

Medical devices labeled as sterile or as having a specific microbial state must be processed, manufactured and, if necessary, sterilized by means of appropriate and validated methods.

9.9

Medical devices intended to be sterilized must be manufactured in appropriate and controlled conditions (e.g. environment).

9.10

Packaging for non-sterile medical devices must be capable of keeping the medical devices at the prescribed level of cleanliness. If medical devices need to be sterilized before use, the packaging system should minimize the risk of microbial contamination with consideration taken of sterilization methods of the medical devices’ owners. Such medical devices must be manufactured in appropriate and controlled conditions.

9.11

The packaging and/or labeling of medical devices must be distinguishable from identical or similar products on the market in both sterile and non-sterile conditions.

10

Manufacturing and environmental characteristics

10.1

If a medical device is intended to be used in combination with other medical devices or tools, the whole combination, including the connection system should be safe and should not impair the specified performance of the medical devices or tools. Any known restrictions on use applying to such combinations should be indicated on the label and/or in the instructions for use.

10.2

Medical devices should be designed and manufactured in such a way as to remove or appropriately reduce:

• risk of injury, related to their physical features, including, as appropriate, mass/pressure ratio, dimensional and design characteristics;

• risks related to reasonably foreseeable external influences or environmental conditions, such as magnetic fields, external electrical and electromagnetic effects, electrostatic discharge, pressure, humidity, temperature or variations in pressure and acceleration;

• risks related to the use of the medical devices when they come into contact with materials, substances or gases, to which they can be exposed during normal conditions of use;

• risks due to accidental penetration of substances into medical devices;

• risks due to incorrect identification of samples;

• risks of interference with other medical devices normally used in investigation or treatment;

• risks arising from failure to maintain or calibrate (as with implantable devices), from aging of the materials used or from the loss of accuracy of some measurement or control mechanism.

10.3

Medical devices must be designed and manufactured in such a way as to minimize the risks of fire or explosion during normal use or in case of malfunction. Particular attention should be paid to medical devices whose intended use includes exposure to or in association with flammable or combustible substances.

10.4

Medical devices should be designed and manufactured in such a way as to facilitate their safe disposal of waste substances.

11

Medical devices with diagnostic or measurement functions

11.1

Medical devices with a measuring function should be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose. The limits of accuracy, correctness and stability should be indicated by the medical devices’ owners.

11.2

Medical devices should be designed and manufactured in such a way as to provide sufficient accuracy, precision and stability for their intended purpose, based on appropriate scientific and technical methods. In particular, the design must address sensitivity, specificity, correctness, repeatability, reproducibility, known confounding factor control, and detection limits, if any.

11.3

In case the operation of medical devices depends on the use of calibration materials and/or control materials, traceability of values assigned to such calibration materials and/or control materials must be ensured through a quality management system.

11.4

Any measurement, monitoring or display scale must be designed in accordance with scientific design principles, taking into account purposes of the medical devices.

11.5

Whenever possible, values expressed numerically should be in commonly accepted, standardized units, and understood by users of the medical devices.

12

Protection against radiation

12.1.

Overview

Medical devices should be designed, manufactured and packaged in such a way that exposure of patients, users and other persons to radiation is appropriately minimized in a manner that is compatible with the intended purpose, whilst not restricting the application of levels for diagnostic and therapeutic purposes.

12.2.

Intended radiation

12.2.1

In case the medical devices are intended to emit hazardous or potentially hazardous radiation, visible and/or invisible to users, for a specific medical purpose, whose benefits to be gained are considered to outweigh the inherent risks, and users can control such radiation, these medical devices should be designed and manufactured to ensure reproducibility of relevant variable parameters within an acceptable tolerance.

12.2.2

In case the medical devices are intended to emit hazardous or potentially hazardous radiation, accessible and/or inaccessible to users, they should be fitted with visual displays and/or audible warnings of such emissions.

12.3.

Unintended radiation

Medical devices should be designed and manufactured in such a way that the exposure of patients, users and other persons to the emission of unintended, stray or scattered radiation is appropriately reduced as far as possible.

12.4

Instructions for use

Instructions for use for medical devices emitting radiation should contain detailed information as to the nature of the emitted radiation, the means of protecting the patients and users, and ways of avoiding misuse and of eliminating the risks during installation.

12.5

Ionizing radiation.

12.5.1

Medical devices emitting ionizing radiation should be designed and manufactured to ensure that the shape, quantity and distribution of energy (or quality) of such emitted radiation can be changed and controlled where possible, taking into account the intended use.

12.5.2

Medical devices emitting ionizing radiation intended for diagnostic X-rays should be designed and manufactured in such a way as to achieve an image and/or output quality that are appropriate to the intended medical purpose whilst minimizing radiation exposure of patients and users.

12.5.3

Medical devices emitting ionizing radiation intended for therapeutic X-rays shall be designed and manufactured in such a manner as to properly monitor and control doses used, beam types, energy and, where possible, monitor and control the energy distribution of radiant beams.

13

Requirements for medical devices connected to or equipped with an energy source.

13.1

Medical devices that incorporate programmable electronic systems, including software, should be designed to ensure the repeatability, reliability and operability of these systems according to their intended use. In case of a single fault state in the system (SFC), appropriate means shall be used to eliminate or appropriately reduce the risks as for as possible.

13.2

For medical devices combined with medical software or being medical software by themselves, such software must be evaluated on an advanced scientific-technical basis, taking into account the principles of development life cycle, risk management, evaluation and verification.

13.3

Medical devices for which the patients' safety depends on an internal power source must be equipped with a power status indicator.

13.4

Medical devices for which the patients' safety depends on an external power supply must be equipped with an alarm system to signal in case of power failure.

13.5

Medical devices intended to monitor one or more clinical parameters of patients must be equipped with an appropriate alarm system to alert users to situations that could lead to death or serious deterioration of the patients' health status.

13.6

Medical devices shall be designed and manufactured to appropriately minimize as far as possible risks of generating large amounts of electromagnetism that could impair the operation of the medical devices themselves or other medical devices located nearby.

13.7

Medical devices must be designed and manufactured to ensure immunity to electromagnetic interference so that these devices can function as intended.

13.8

Protection against electrical risks

Medical devices must be designed and manufactured in such a way that patients or anyone else are protected in the best way against electrocution accidents when such devices are installed and maintained in accordance with the owners' instructions, in a normal operating condition and in a single fault condition (SFC)

14

Protection against mechanical risks

14.1

Medical devices must be designed and manufactured to protect patients and users against mechanical risks connected with their use.

14.2

Medical devices shall be designed and manufactured to minimize risks arising from vibrations generated by the medical devices, taking account of technical progress and of the means available for limiting vibrations, particularly at source, unless the vibrations are part of the operation of the devices.

14.3

Medical devices shall be designed and manufactured to minimize risks arising from the noise emitted, taking account of technical progress and of the means available to reduce noise, particularly at source, unless the noise emitted is part of the operation of the devices.

14.4

Terminals and connectors to user-controlled electrical, gas, or hydraulic and pneumatic power supplies shall be designed and constructed to minimize any possible risks.

14.5

Accessible parts of medical devices (excluding the parts or areas intended to supply heat or reach given temperatures) and their surroundings should not attain dangerous temperatures under normal conditions of use.

15

Protection against risks to the patient by the supply of energy or substances

15.1

Medical devices for supplying patients with energy or substances should be designed and installed in such a way that the rate and/or amount to be delivered can be set and maintained accurately enough to ensure the safety of patients and users.

15.2

Medical devices should be fitted with means of preventing and/or indicating any inadequacies in the rate and/or amount of energy delivered or substances delivered which could pose a danger. Medical devices should be equipped with suitable means to prevent, as far as possible, the accidental release of energy or substances at dangerous levels.

15.3

The control and indicator display functions must be clearly specified on medical devices. In case a medical device bears instructions required for its operation or indicates operating or adjustment parameters by means of a visual system, such information should be understandable to users and, as appropriate, patients.

16

Active implantable medical devices

16.1

Active implantable medical devices must have clear information to determine:

• Categories of medical devices;

• Medical devices’ owners; and

• Year of manufacture of medical devices.

16.2

That information must be readable without surgery on transplant recipients.

17

Protection against risks for patients posed by medical devices for use or testing by lay users

17.1

These medical devices shall be designed and manufactured so that they perform in a manner suitable for their intended purpose, taking into account the existing skills and facilities of the user and the effects from variations that can be reasonably anticipated in terms of the user's technology and environment. The information and instructions provided by the medical device owner must be easy for the user to understand and apply.

17.2

These medical devices must be designed and manufactured in such a way as to minimize risks of error during use, and if applicable, in the handling of testing samples and in the interpretation of testing results.

17.3

These medical devices should, where appropriate, include a means by which the lay users can verify that, at the time of use, the medical devices will perform as intended by the owners.

18

Information provided by medical devices’ owners

Users must be provided with information necessary to identify medical devices, owners of medical devices, explanations for use of medical devices in a safe manner, etc.

19

Clinical investigation

Clinical investigations conducted on human subjects must be based on the Declaration of Helsinki. This requirement covers all steps in a clinical investigation from initial consideration of the need and justification of the investigation to the publication of results.