Decision 2426/QD-BYT 2021 Guidance for preparation of ASEAN common submission dossiers

DECISION

On promulgation of Guidance for preparation of ASEAN common submission dossiers

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THE MINISTER OF HEALTH

Pursuant to the Government’s Decree No. 75/2017/ND-CP dated June 20, 2017, defining the functions, tasks, powers and organizational structure of the Ministry of Health;

Pursuant to the Government's Decree No. 36/2016/ND-CP dated May 15, 2016, on medical equipment management;

Pursuant to the Government’s Decree No. 169/2018/ND-CP dated December 31, 2018, on amending and supplementing a number of articles of the Government’s Decree No. 36/2016/ND-CP dated May 15, 2016, on medical equipment management;

Pursuant to the Government’s Decree No. 03/2020/ND-CP dated January 01, 2020 on amending and supplementing Article 68 of the Government’s Decree No. 36/2016/ND-CP dated May 25, 2016, on medical equipment management, which was amended and supplemented under the Government’s Decree No. 169/2018/ND-CP dated December 31, 2018, on amending and supplementing a number of articles of the Government's Decree No. 36/2016/ND-CP dated May 15, 2016, on medical equipment management;

At the proposal of the Director of the Department of Medical Equipment and Construction;

DECIDES:

Article 1. Scope of regulation

To promulgate together with this Decision the ASEAN common submission dossier template, applicable to the dossiers for circulation registration numbers for type-B, -C and -D medical devices.

Article 2. Effect

This Decision takes effect on the date of promulgation.

Article 3. Implementation organization

Chief of the Ministry Office, Chief of the Ministry Inspector, Directors and Director Generals of the Ministry of Health, Directors of Health Departments of provinces and centrally-run cities, and relevant agencies, organizations and individuals shall implement this Decision.

Any difficulties arising in the course of implementation should be promptly reported to the Ministry of Health for consideration and settlement./.

ASEAN COMMON SUBMISSION DOSSIER TEMPLATE

(Attached to the Minister of Health’s Decision No. 2426/QD-BYT dated May 15, 2021)

ASEAN COMMON SUBMISSION DOSSIER

Name of the facility registering the circulation of medical device (hereinafter referred to as registrant) (name and address)

The registrant undertakes that the following statements are true and that it takes full responsibility before the law for them:

1. General summary

1.1. Brief and general description of medical device

General description of medical device includes: descriptive information, introduction to the medical device, purposes and indications for use, new features if any (for example, whether nano technology or artificial intelligence is used, etc.)

1.2. Commercial marketing history

Provision of a list of countries where the device has been marketed, along with the year (if any) of starting selling in that market.

1.3. Intended use and indications

Intended use and indications for use of the medical device shown on the label or instructions for that medical device.

1.4. Licensing information for circulation in different countries

Provision of information on device licensing status in the following countries: EU member countries, Japan, Canada, Australia (TGA), USA (FDA), UK, Switzerland including licensing status (approved, awaiting approval, refused, not registered for circulation, etc.), intended use, indications, date of first licensing¹.

This information may be provided in a tabular format as given below:

Provision of copies (or links for online search) of documents for licensing the circulation on the above-mentioned countries (if any).

1.5. Important safety or performance information of the medical device

Provision of summary information about adverse events that have occurred and corrective actions to ensure safety in the market since the medical device was introduced to the market or in the last 5 years.

Summary information about adverse events that have occurred should include, at a minimum, a description of the adverse event, the number of adverse events, or the frequency of occurrence (i.e., the total number of adverse events recorded in total number of medical devices sold). This information may be provided in a tabular format as given below:

Information about corrective actions to ensure safety in the market, at least including date of occurrence, description of the event, name of the country or territory taking the corrective action. This information may be provided in a tabular format as given below:

If there have been no adverse events or corrective actions since the medical device circulation or in the last 5 years, a written confirmation from the device owner is required.

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

• Human or animal cells, tissues or their derivatives are used in non-living form, for example artificial heart valves originating from pigs, catgut, etc.

• Cells, tissues or derivatives of microbial or recombinant origin, for example skin plumping devices based on hyaluronic acid obtained by bacterial fermentation.

• Containing a radiation component, ionizing (e.g. X-ray), or non-ionizing (e.g. laser, ultrasound, etc.).

2. Table of conformity to the essential principles (may be in Vietnamese or English)

The table of conformity to the essential principles of medical device safety and performance issued by the medical device owner may be provided as described in the attached Appendix to demonstrate the device in compliance with relevant essential principles.

Where medical devices have been licensed for circulation in EU member states, a table of conformity with essential principles according to EU regulations can be provided.

3. Medical device description

3.1. Medical device description and features

Providing a more detailed description of the medical device attributes to explain how the device functions, the basic scientific concepts that form the fundamentals for the medical device, the component materials and accessories used in its principles of operation as well as packaging. A complete description of each functional component, material or ingredient of the medical device should be provided, with labeled pictorial representation of the device in the form of diagrams, photographs or drawings, as appropriate.

3.2. Intended use

The use for which the medical device is intended, for which it is suited according to the data supplied by the medical device owner in the instructions as well as the functional capability of the medical device.

3.3. Indications

A general description of the disease or condition that the medical device will diagnose, treat, prevent, cure or mitigate and includes a description of the target patient population for which the medical device is intended.

3.4. Instructions for use

All necessary information from the device owner, including the procedures, methods, frequency, duration, quantity and preparation to be followed for safe use of the medical device.

3.5. Contraindications

Information about cases where the medical device should not be used for patient safety reasons, for example:

 due to medical history, physiological characteristics of the patient, etc. in accordance with the information written on the label or instructions of the medical device.

This is a general description of the disease or condition and the patient population for which the medical device should not be used for the purpose of diagnosing, treating, curing or mitigating. Contraindications are conditions under which the medical device should not be used because the risk of use clearly outweighs any possible benefit.

3.6. Warnings

This is the specific hazard alert information that a user needs to know before using the medical device.

3.7. Precautions

This alerts the user to exercise special care necessary for the safe and effective use of the medical device. They may include actions to be taken to avoid effects on patients/users that may not be potentially life-threatening or result in serious injury, but about which the user should be aware. Precautions may also alert the user to adverse effects on the medical device of use or misuse and the care necessary to avoid such effects.

3.8. Potential adverse effects

These are potential undesirable and serious outcomes (death, injury, or serious adverse events) to the patient/user, or side effects from the use of the medical device, under normal conditions.

3.9. Alternative therapy

This is a description of any alternative practices or procedures for diagnosing, treating, curing or mitigating the disease or condition for which the medical device is intended.

3.10. Materials (may be in Vietnamese or English)

A description of the materials of the medical device and their physical properties to the extent necessary to demonstrate conformity with the relevant Essential Principles.

For a medical device other than in vitro diagnostic medical devices:

- List of materials of the medical device making either direct (e.g. with the mucous membrance) and or indirect (e.g. during extracorporeal circulation of body fluids) with the human body, enclosed their chemical, biological and physical properties.

- For medical device intended to emit ionizing radiation, information on the radiation source (e.g. radioisotopes) and the material used for shielding of unintended radiation from users and patients shall be provided.

- Where there are specific concerns related to the safety of materials used in the medical device, e.g. impurities, residue levels and exposure to plasticizers such as Bis(2-ethylhexyl) phthalate (DEHP), it is necessary to additionally provide a certificate of raw material in conformity with relevant standards, analysis certificate, or risk assessment on the safety of the materials used. 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 device.

For in vitro diagnostic reagents, calibrators and control materials:

- Provide the list of materials used for manufacture of the medical device, including the material name, role in finished product.

- Provide information about the composition, biological properties, and origin of the materials involved in the reaction for testing: antigens, antibodies, enzymes, conjugates, PCR primers, probes, calibrators, controls, etc.

- For medical device containing substances subject to special control (narcotics or radiation-generating materials, non- ionizing or ionizing), full information on ingredients, content and role of these substances, for example Buprenorphine in the drug testing kit, Iodide-131 in the Radioimmunoassay kit, radio-labeled Phosphorus-32 DNA probes in Southern blots), etc. must be provided.

- For in vitro diagnostic medical device of types C, D: information about standards or test reports of materials participating in the reaction (except stabilizers) must be provided. The information is presented for each active material (antigen, antibody, conjugate, etc.).

3.11. Other relevant specifications

The functional characteristics and technical performance specifications for the medical device including, as relevant, accuracy, sensitivity, specificity of measuring and diagnostic medical devices, reliability and other factors; and other specifications including chemical, physical, electrical, mechanical, biological, software, sterility, stability, storage and transport, and packaging to the extent necessary to demonstrate conformity with the relevant Essential Principles.

3.12. Other information

Other important descriptive characteristics not detailed above, to the extent necessary to demonstrate conformity with the relevant Essential Principles (for example, the biocompatibility category for the medical device, etc.).

Note: In case the above information is stated in the instructions, reference may be made to the instructions.

4. Summary of design verification and validation documents (may be in Vietnamese or English)

This section should summarize or reference or contain design verification and design validation data to the extent appropriate to the complexity and risk class of the medical device.

Such documentation should typically include:

• Declarations or certificates of conformity to the “recognized” standards listed as applied by the product owner; and/or

• Summaries or reports of tests and evaluations based on other standards, manufacturer methods and tests, or alternative ways of demonstrating compliance.

For example: The completed table of conformity to the essential principles mentions that manufacturer uses a recognized standard was to demonstrate conformity to one Essential Principle, a declaration of conformity to the standard, or a certification of conformity, and a summary of the test data, if the standard does not include performance requirements, must be provided.

The data summaries or tests reports and evaluations would typically cover, as appropriate to the complexity and risk class of the medical device:

- A listing of and conclusions drawn from published reports that concern the safety and performance of aspects of the medical device with reference to the Essential Principles;

- Engineering tests;

- Laboratory tests;

- Biocompatibility tests;

- Animal tests;

- Simulated use;

- Software validation.

4.1. Pre-clinical studies

Details must be provided on all biocompatibility tests conducted on materials used in a medical device All materials that are significantly different must be characterized. Information describing the tests, the results and the analyses of data must be presented.

Complete pre-clinical physical test data must be provided, as appropriate. The report must include the objectives, methodology, results and product owner’s conclusions of all physical studies of the medical device and its components. Physical testing must be conducted to predict the adequacy of medical device response to physiological stresses, undesirable conditions and forces, long-term use and all known and possible failure modes.

Pre-clinical animal studies used to support the probability of effectiveness in humans must be reported. These studies must be undertaken using good laboratory practices. The objectives, methodology, results, analysis and product owner’s conclusions must be presented. The study conclusion should address the medical device’s interactions with animal fluids and tissues and the functional performance of the medical device in the experimental animal model(s). The rationale (and limitations) of selecting the particular animal model should be discussed.

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

For sterilized medical device, sterilization appraisal reports must be provided. If the sterilant is toxic or produces toxic residuals (e.g. ethylene oxide residuals), test data and methods that demonstrate that post-process sterilant or residuals are within the acceptable limits must be presented.

For net-work connected, Internet-connected and wireless enable medical devices, evidence supporting the cyber security of such devices shall be provided. For example: analyzing risks and possibilities of cyber-attacks, cyber security control methods, plans, processes or mechanisms to monitor, promptly detect and manage security-related threats during the shelf life of the medical device. A declaration from the manufacturer or owner stating that the medical device is connected to the network, Internet or it is a wireless enable device, ensuring cyber security.

4.1.1. Software verification and validation studies (if applicable)

The correctness of a software product is another critical product characteristic that cannot be fully verified in a finished product. The product owner must provide evidence that validates the software design and development process. This information should include the results of all verification, validation and testing performed in-house and in a user’s environment prior to final release, for all of the different hardware configurations identified in the labeling or the instructions, as well as representative data generated from both testing environments.

4.1.2. Medical devices containing biological materials

Results of studies substantiating the adequacy of the measures taken with regards to the risks associated with transmissible agents must be provided. This will include viral clearance results for known hazards. Donor screening concerns must be fully addressed and methods of harvesting must also be fully described. Process validation results are required to substantiate that manufacturing procedures are in place to minimize biological risks.

4.2. Pre-clinical studies for in vitro diagnostic reagents, calibrators and control materials

4.2.1. Analytical performance

Provision of research reports on the analytical performance of the medical device, including analytical sensitivity, analytical specificity, limit of detection (LOD), limit of quantification (LOQ), linearity, detection range, precision, repeatability, influencing factors, durability, etc. Performance criteria will depend on each medical device.

Information about samples used for evaluation (negative and positive control samples, baseline standard samples, standard panels, influencing substances, etc.).

Research reports should include the objectives, methods, results, and conclusions of the research. The results and conclusions must clearly demonstrate that the product has characteristics suitable for its intended use.

4.2.2. Stability

Provision of stability study reports, including real-time stability and stability under accelerated aging conditions (as appropriate). In cases where real- time stability study is not performed but only under accelerated aging conditions, a full and reasonable explanation is required.

Provision of in-use stability study reports for products that are used multiple times after opening.

Stability study reports during transportation, performed under real or simulated conditions shall be provided.

Stability study reports should include the objectives, methods, results, and conclusions.

4.3. Clinical evidence

A clinical evaluation report of the medical device should be provided. Where applicable, this evaluation may take the form of a systematic review of existing bibliography, clinical experience with the same or similar medical devices, or by clinical investigation. Clinical investigation is most likely to be needed for higher risk class medical devices, or for medical devices where there is little or no clinical experience.

The clinical evaluation report should include the purpose and context of the clinical evaluation, clinical input data, data evaluation and analysis, and conclusions regarding the safety and performance of the medical device.

The clinical evaluation report should have all the necessary information as an independent document for review by regulatory agencies. This should summarize:

- The technology used by that medical device, indications, statements about the safety and clinical performance of that medical device, if any.

- Nature, scope and scale of clinical data assessed.

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

4.3.1. Use of existing bibliography

Copies are required of all literature studies, or existing bibliography, that the product owner is using to support safety and effectiveness.

Clinical evidence of effectiveness may comprise medical device-related investigations conducted domestically or other countries. It may be derived from relevant publications in international medical journals. The documented evidence submitted should include the objectives, methodology and results presented in context, clearly and meaningfully. Before drawing conclusions about the results of clinical investigation, there must be a discussion in context with the published literature.

4.3.2. Use of clinical experience

Clinical experience refers to clinical data obtained from clinical use of the product, not from clinical investigations. Clinical experience may be with the same product or a similar product.

Clinical experience may be obtained from the following data:

- Post-marketing surveillance reports from product owners, regulatory agencies, cohort studies (may contain unpublished long-term study data on safety and effectiveness).

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

- Data from patients using the medical device in the aid program before marketing the product.

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

4.3.3. Use of clinical investigations

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

A clinical investigation may be conducted by the medical device owner or by a third party on behalf of the owner. Clinical investigations should be designed, performed and reported in accordance with ISO 14155, Parts 1 and 2, Clinical Investigations of Medical Devices for Human Subjects, or in accordance with an equivalent standard, and in compliance with local regulations.

Clinical investigations shall be carried out in accordance with the ethical principles laid down in the Helsinki Declaration.

For in vitro diagnostic medical devices: Clinical investigation is performed to establish or confirm the clinical performance of in vitro diagnostic medical devices. The manufacturer must have clinical evidence supporting its clinical claims, including diagnostic sensitivity (clinical sensitivity) and diagnostic specificity (clinical specificity).

5. Medical device labeling

This is the descriptive and informational product literature that accompanies the medical device any time while it is held for sale or shipped, including instructions, pack labeling. This section should summarize or reference or contain the following labeling data to the extent appropriate to the complexity and risk class of the medical device, which is generally considered as “labeling”:

• Labels on the medical device and its packaging;

• Instructions for use;

• Any information and instructions given to the patient, including instructions for any procedure the patient is expected to perform (if applicable).

5.1. Samples of labels on the medical device and its packaging

This is the printed, written or graphic product information provided on or attached to one or more levels of packaging, including the outer packaging or the outside container wrapper. If it is physically impossible to include samples of labels (e.g. large warning labels affixed onto an X-ray machine), alternative submission methods (e.g. photographs or technical drawings), to the extent appropriate, will suffice to meet the requirements of this section.

The samples of labels must meet requirements in accordance with the applicable laws. For an imported medical device, the label sample must include both the original label and the supplementary label in Vietnamese language.

The label sample must include all products in the circulation registration dossier. In case the dossier is submitted according to the medical device family, a representative label sample can be submitted but must note the differences between the label samples of those products.

5.2. Instructions for use in Vietnamese language

The instructions for use contain directions under which the physician or end-user can use a medical device safely and for its intended purpose. This should include information on indications, contraindications, warnings, precautions, potential adverse effects, alternative therapy and the conditions that should be managed during normal use to maintain the safety and effectiveness of the medical device.

For in vitro diagnostic medical devices, the instructions for use should contain the following information:

- Type and code (if any) of the in vitro diagnostic medical device.

- Intended use:

• To detect or measure something;

• Medical device functions (e.g. screening, monitoring, diagnosis or supporting diagnosis, prognosis, prediction);

• Use the same medical device (testing machine) whether automated or non-automated;

• Quantitative or semi-quantitative or qualitative or nominal, etc.;

• Type of sample used in the test (e.g. serum, plasma, whole blood, tissue biopsy, urine);

• Test population.

- Instructional information: product used in in vitro diagnostics.

- Users (e.g. laypersons, medical staff, etc.).

- Principle of testing.

- Description of reagents, calibrators, standards, control materials and limitations on their use (e.g. only suitable for use with a specific testing machine).

- List of materials provided and list of materials specifically requested but not provided.

- For in vitro diagnostic medical device used in combination with other medical devices and/or in combination with non-medical devices:

• Information to identify these devices or equipment, including important performance characteristics.

• Information on known limitations associated with that device or equipment.

- Special storage conditions (e.g. temperature, light, humidity), conditions when using the medical device, if relevant.

- Stability during use, which may include storage conditions and shelf life after first opening; storage conditions and stability of working solutions, as appropriate. The instructions for use must clearly state the product's lifespan.

- If the medical device is provided as sterile, it is necessary to clearly state the medical device 's sterility, sterilization method, and instructions for handling in case the sterile packaging is damaged before use.

- Information to enable the user to be informed of any warnings, precautions, measures to be taken and limitations on use of the in vitro diagnostic medical device. This information should include, as appropriate:

• Warnings, precautions and/or measures to be taken in the case of in vitro diagnostic medical device damage or deterioration reflected through a change in the appearance of the medical device that may affect performance;

• Warnings, precautions and/or measures to be taken regarding exposure to foreseeable external influences or environmental conditions, such as external magnetic, electrical and electromagnetic fields, electrical discharge, radiation related to diagnostic or therapeutic procedures, pressure, humidity or temperature;

• Warnings, precautions and/or measures to be taken regarding possible risks during the use of the medical device for specific diagnosis, evaluation, treatment (e.g. electromagnetic interference emitted by the device, affecting other devices);

• Precautions regarding materials incorporated into the medical device that contain carcinogenic, mutagenic or reproductively harmful substances, endocrine disruptors, or other substance that may cause sensitivity or allergy in the patient or user.

- Conditions for collecting, manipulating and preparing samples

- Instructions for preparing or handling the medical device before use, such as sterilization, assembly, calibration, etc., so that the device is used as intended by the owner.

- Information needed to determine when the in vitro diagnostic medical device is properly installed and ready to perform safely and as intended by the owner, along with the following information, when relevant:

• Details of the nature and frequency of preventive and routine maintenance, including cleaning or disinfection;

• Consumables and instructions to replace them;

• Information about the calibrations that need to be performed to ensure the medical device operates properly and safely throughout its life cycle;

• Measures to reduce the risk to persons involved in the installation, calibration or repair of, for example, contaminated surfaces.

- Recommendations on quality control procedures, if necessary.

- Instructions on how to retrieve the values assigned to calibrators and control materials, including information to identify reference materials and reference measurement procedures used.

- Test procedure, including calculation and interpretation of results, and recommendation of additional confirmatory testing if appropriate.

- Analytical performance characteristics, such as sensitivity, specificity and precision (which is a combination of accuracy and precision).

- Clinical performance characteristics, such as diagnostic sensitivity and diagnostic specificity, if relevant.

- Reference intervals, if relevant.

- Information on interferences or limitations (e.g. visual evidence of hyperlipidemia or hemolysis, specimen storage duration) that may affect the performance of the analysis.

- Warnings or precautions to be taken regarding disposal of the device, accessories and consumables used together, if any. This information should include, as appropriate:

• Bacterial or microbial contamination hazards (e.g. consumable materials contaminated with potentially infectious substances of human origin);

• Environmental hazards (e.g. batteries or materials that emit potentially dangerous levels of radiation);

• Physical hazards (e.g. explosion).

- For in vitro diagnostic medical device used by layperson, users should be advised to consult a health care professional before making any medical decisions.

- References, if relevant.

- Name and address of the owner in a format that is identifiable and allows identification of information about the owner. In case the instructions for use contain information about the manufacturing facility and origin, this information must include complete information about the name and address of the manufacturer.

- Document identification information, such as version number or release date.

6. Risk analysis (may be in Vietnamese or English)

This section should summarize or reference or contain the results of the risk analysis. This risk analysis should be based upon international or other recognized standards, and be appropriate to the complexity and risk class of the medical device.

6.1. Results of risk analysis

A list of possible hazards for these medical devices shall be provided. Indirect risks from medical devices may result from medical device-associated hazards, such as moving parts, which lead to sustained injury, or from user-related hazards, such as ionizing radiation from an X-ray machine. The evaluation of these risks against the claimed benefits of the medical device and the method(s) used to reduce risk to acceptable levels must be described. The individual or organization that carries out the risk analysis must be clearly identified. The technique used to analyze risk must be specified, to ensure that it is appropriate for the medical device and the risk involved.

7. Manufacturing information (may be in Vietnamese or English)

This section should summarize or reference or contain documentation related to the manufacturing processes, including quality assurance measures, which is appropriate to the complexity and risk class of the medical device.

7.1. Manufacturer information

List the names and addresses of all manufacturers involved in the manufacturing and sterilization process (including third-party manufacturers and sterilizers).

7.2. Manufacturing process

Information on the manufacturing process shall be provided in sufficient detail to allow a general understanding of the manufacturing processes. Detailed proprietary information on the manufacturing process is not required. The information may be presented in the form of a process flow chart showing an overview of production, controls, assembly, in-process and final product testing, and packaging of the finished 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.

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¹ For products licensed for circulation in EU member countries, if there is no information on the date of first licensing, the most recent licensing date may be recorded.