Chương II Thông tư 32/2018/TT-BYT: Yêu cầu về dữ liệu lâm sàng để bảo đảm an toàn, hiệu quả và tiêu chí xác định trường hợp miễn thử, miễn một số giai đoạn thử thuốc trên lâm sàng, thuốc phải thử lâm sàng giai đoạn 4 tại việt nam

Chapter II

MANDATORY CLINICAL DATA FOR ASSURANCE OF SAFETY AND EFFICIACY; CRITERIA FOR EXEMPTION FROM CLINICAL TRIAL OR CERTAIN STAGES THEREOF IN VIETNAM; DRUGS THAT HAVE TO UNDERGO STAGE 4 CLINICAL TRIAL

Article 13. Clinical data in an application for marketing authorization of a new modern drug, vaccine or biological

1. Mandatory clinical data in an application for marketing authorization of a new modern drug, vaccine or biological

a) Clinical studies of the drug, data in clinical documents shall be conformable with ICH guidelines, the Ministry of Health of Vietnam or guidelines of other organizations recognized by Vietnam (international organizations to which Vietnam is a member, reference agencies specified in Clause 9 Article 2 of this Circular), except for the case specified in Clause 2 of this Article;

b) Clinical database (except similar biologicals and reference biologicals, similar vaccines and vaccines approved for marketing authorization in Vietnam) shall be sufficient for analysis and justification of the safety and efficacy of the drug in Asian populations for extrapolating clinical data from Asian populations according to instructions in Point a Clause 1 of this Article, or bridging study data according to ICH-E5 for extrapolating clinical data from Asian populations;

c) If the vaccine has been approved for market authorization according to Point g Clause 4 Article 23 of this Circular and has sufficient clinical data for safety and efficacy according to Point a and Point b Clause 1 of this Article but its manufacturing process is not entirely carried out in Member States specified in Clause 10 Article 2 of this Circular, it is required to have clinical data pertinent to safety and immunogenicity in the intended population in Vietnam before market authorization

d) If the vaccine has sufficient clinical data for safety and efficacy as prescribed in Point a and Point b Clause 1 of this Article but a requirement specified in Point g Clause 4 Article 23 of this Circular is not satisfied, it is required to have clinical data pertinent to safety and immunogenicity in the intended population in Vietnam before market authorization.

2. If the study is carried out before the effective date of the regulations or instructions mentioned in Point a Clause 1 of this Article, data of the study is acceptable.

Article 14. Mandatory clinical data for safety and efficacy in the application for marketing authorization of a drug with new combination of similar biologicals or active ingredients

1. A drug with new combination of active ingredients shall have sufficient clinical data according to guidelines of US FDA, EMA or WHO for clinical development of fixed-dose combinations according to Appendix IV hereof.

2. Similar biologicals shall have sufficient clinical data according to the guideline of the Ministry of Health or WHO for development of similar biologicals. Guidelines of US FDA and EMA that are developed based on the aforementioned guidelines are acceptable. Guidelines of WHO, US FDA, EMA are provided in Appendix IV hereof.

Article 15. Mandatory clinical data for safety and efficacy in the application for marketing authorization of a new non-proprietary drug

1. If the drug that has been approved for market authorization in its home country is a prescription drug (except drugs manufactured in Vietnam) and at least a similar drug (with the same active ingredient, content, concentration thereof, dosage form and route of administration) has been approved for market authorization by one of the regulatory bodies specified in Clause 10 Article 2 of this Circular, the clinical data shall satisfy one of the following requirements:

a) The use of clinical data of the similar drug is permitted by its owner. The clinical data shall satisfy the requirements in Article 13 of this Circular;

b) There is clinical data from published researches and bioequivalence studies (unless the drug does not require bioequivalence test according to regulations of the home country).

2. If the drug that has been approved for market authorization in its country of origin is a prescription drug (except drugs manufactured in Vietnam and the case specified in Clause 3 of this Article) and at least a similar drug (with the same active ingredient, content, concentration thereof, dosage form and route of administration) has been approved for market authorization by one of the regulatory bodies specified in Clause 10 Article 2 of this Circular, the clinical data shall satisfy one of the following requirements:

a) The use of clinical data of the similar drug is permitted by its owner. The clinical data shall satisfy the requirements in Article 13 of this Circular;

b) There is clinical data from published researches and bioequivalence studies (unless the drug does not require bioequivalence test according to regulations of the country of origin).

3. If the drug that is approved for marketing authorization is classified as non-proprietary by one of the reference authorities mentioned in Clause 9 Article 2 of this Circular, it is required to have justification and evidence that the use of the active ingredients (indications, dose, route, users) is specified in Vietnam’s National Pharmacopoeia, other pharmacopoeia accepted by any of the reference authorities specified in Clause 9 Article 2 of this Circular.

Article 16. Mandatory clinical data for safety and efficacy in the application for marketing authorization of a new drug with content, concentration, dose, route, indications or intended users that are different from the proprietary drug which has been approved for market authorization in Vietnam

Clinical documents specified in Article 13 of this Circular are mandatory for a modern drug whose content, concentration, dose, route, indications or intended users that are different from the proprietary drug which has been approved for market authorization in Vietnam, or has a new dosage form that might affect its biopharmaceutics.

Article 17. Mandatory clinical data for drugs approved for marketing authorization in Vietnam in case of changes in clinical data thereof

In case of changes to clinical data for a modern drug, vaccine, biological or herbal drug that has been approved for marketing authorization in Vietnam, the applicant shall provide the additional clinical data in accordance with Appendix II of this Circular.

Article 18. Criteria for exemption of one or some stages of clinical trial of new modern drugs, vaccines, biologicals before marketing authorization

In one of the following cases, the Ministry of Health is entitled to exempt one or several stages of clinical trial (including clinical data) of a drug that fails to meet the requirements specified in Article 13 of this Circular on the basis of opinions given by the Advisory Board:

1. The drug is meant to serve urgent needs for national defense and security, epidemic control, disaster relief and cannot be replaced by any other drug on the market.

2. The drug is approved for market authorization by at least two of the reference authorities specified in Clause 9 Article 2 of this Circular, or approved for market authorization by US FDA or EMA based on the reduced clinical documents they require.

3. The drug is meant to treat a rare or fatal disease.

4. Vaccines and biologicals manufactured in Vietnam through technology transfer of one, some or all of the manufacturing processes of the finished vaccine or biological whose clinical data satisfies the requirements in Clause 1 Article 13 and Article 14 of this Circular.

Article 19. Mandatory clinical data in an application for marketing authorization a new herbal drug

1. Mandatory clinical data for assurance of safety and efficacy in the application; for marketing authorization a new herbal drug:

a) Clinical studies of the drug, data in clinical documents shall be conformable with guidelines of the Ministry of Health of Vietnam or other organizations recognized by Vietnam, including: WHO’s Research guidelines for evaluating the safety and efficacy of herbal medicines or guidelines of a regulatory body specified in Clause 10 Article 2 of this Circular. If the study is carried out before the effective date of the aforementioned regulations or instructions, data of such study is acceptable;

b) Data extracted from the following documents is acceptable as clinical data for consideration of safety and efficacy of the drug:

- The treatises about safety and efficacy of the drug mentioned in pharmacopoeias of Vietnam and other countries;

- Evaluations of safety and efficacy of the drug published on SCI (Science Citation Index) journals and clinical data collected from other medical publications;

- Evaluations of safety and efficacy in a national, ministerial or provincial research which has been accepted.

2. Clinical data mentioned in Clause 1 of this Article is not required if the herbal drug satisfies any of the following requirements:

a) The drug has the same composition, content of herbal ingredients, indications and route of administration as those of another herbal drug which has been approved for marketing authorization (even if it has expired) except traditional drugs the indications of which do not include any of the diseases on the list of diseases published by the Ministry of Health according to Point b Clause 1 Article 89 of the Law on Pharmacy;

b) The drug has the same composition, content of herbal ingredients, indications and route of administration as those of another herbal drug which has been approved for marketing authorization in Vietnam for at least 05 years, has sufficient clinical data as prescribed in Clause 1 of this Article and is not meant to treat the diseases on the list of diseases published by the Ministry of Health according to Point b Clause 1 Article 89 of the Law on Pharmacy.

Article 20. Criteria for exemption of one or some stages of clinical trial of herbal drugs before marketing authorization

In one of the following cases, the Ministry of Health is entitled to exempt one or several stages of clinical trial (including clinical data) of a herbal drug that fails to meet the requirements specified in Article 19 of this Circular on the basis of opinions given by the Advisory Board:

1. The drug is meant to serve urgent needs for national defense and security, epidemic control, disaster relief and cannot be replaced by any other drug on the market.

2. The drug is approved for market authorization by at least one of the reference authorities specified in Clause 9 and Clause 10 Article 2 of this Circular according to the reduced clinical documents they require.

3. The drug is meant to treat a disease on the list of diseases published by the Minister of Health according to Point b Clause 1 Article 89 of the Law on Pharmacy but is not exempt from clinical trial as prescribed in Clause 3 Article 21 of this Circular.

4. The drug is new combination of herbal ingredients that have been used in Vietnam and the indications of which do not include any of the diseases on the list of diseases published by the Minister of Health according to Point b Clause 1 Article 89 of the Law on Pharmacy.

Article 21. Criteria for exemption of clinical trial in Vietnam before marketing authorization

1. A generic drug has the same active ingredients, content and concentration thereof, route of administration, uses, doses, indications, intended users and dosage form as those of another drug that has been approved for market authorization.

2. A new drug (except vaccines), has been approved for market authorization in at least another country and has sufficient clinical data according to Article 13 and Article 19 of this Circular.

3. An herbal drug is granted the marketing authorization before the effective date of the Law on Pharmacy and the indications of which do not include any of the diseases on the list of diseases published by the Ministry of Health.

4. A vaccine has been approved for market authorization and satisfies the requirements specified in Point g Clause 4 Article 23 of this Circular, all of the manufacturing processes of which are carried out in the Member States specified in Clause 10 Article 2 of this Circular, and the clinical data is sufficient according to Article 13 of this Circular.

Article 22. When to carry out a State IV clinical trial in Vietnam

The drug has been approved for market authorization but its safety and efficacy needs additional evaluation as proposed by the Advisory Board.