Thông tư 39/2021/TT-BYT sửa đổi Thông tư 21/2018/TT-BYT quy định về việc đăng ký lưu hành thuốc cổ truyền, dược liệu

CIRCULAR

AMENDMENTS TO A NUMBER OF ARTICLES OF CIRCULAR NO. 21/2018/TT-BYT DATED SEPTEMBER 12, 2018 OF THE MINISTER OF HEALTH ON MARKETING AUTHORIZATION OF TRADITIONAL DRUGS AND HERBAL INGREDIDENTS.

Pursuant to the Law No. 105/2016/QH13 on Pharmacy dated April 06, 2016;

Pursuant to the Government’s Decree No. 54/2017/ND-CP dated May 08, 2017 on guidelines for some articles and implementation of the Law on Pharmacy.

Pursuant to the Government’s Decree No. 155/2018/ND-CP dated November 12, 2018 on amendments to some articles related to business conditions under state management of the ministry of health

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

At the request of the Director of the Traditional Medicine Administration of Vietnam;

The Minister of Health promulgates a Circular on amendments to a number of articles of Circular No. 21/2018/TT-BYT dated September 12, 2018 of the Minister of Health on marketing authorization of traditional drugs and herbal ingredients.

Article 1. Amendments to a number of articles of Circular No. 21/2018/TT-BYT dated September 12, 2018 of the Minister of Health on marketing authorization of traditional drugs and herbal ingredients

1. Article 1 shall be amended as follows:

 “This Circular details the following contents:

1. Cases of traditional drugs that the Ministry of Health recognizes exemption from clinical trials; criteria for identification of cases of exemption from some stages of clinical trials, cases of phase 4 clinical trials, cases of clinical trials with full stages and requirements for clinical data for the purpose of assurance about safety and effectiveness in the marketing application of traditional drugs.

2. Applications and procedures for issuance, extension, amendments to marketing authorization of traditional drugs and herbal ingredients.

3. Withdrawal of marketing authorization of traditional drugs and herbal ingredients

4. Advisory council that issues marketing authorization of traditional drugs and herbal ingredients (hereinafter referred to as “ the advisory council”) and experts who appraise marketing application of traditional drugs and herbal ingredients.”

2. Clauses 2, 3 Article 3 shall be amended as follows:

 “2. Ancient remedy means a remedy recorded in a book on traditional medicine or a remedy recorded in the Pharmacopoeias of countries that have been compiled and promulgated by the Ministry of Health in the List of ancient remedies.

3. Dose-adjusted remedy means an ancient remedy with an increase or decrease in the number of ingredients and the content of each ingredient in order to increase the effectiveness of treatment and reduce the toxicity of the remedy in accordance with the disease according to theory of traditional medicine."

3. Clauses 6, 7 and 8 Article 3 shall be amended as follows:

 “ 6. Major variations mean changes that clearly and directly impact on the quality, safety and effectiveness of traditional drugs and herbal ingredients specified in Appendix II issued together with this Circular.

7. “ Minor variations mean changes that have no impact or have little impact on the quality, safety and effectiveness of traditional drugs and herbal ingredients specified in Appendix II issued together with this Circular.

8. Certificate of Pharmaceutical Product (hereinafter referred to as “CPP”) is a certificate issued under the certification scheme on the quality of pharmaceutical products moving in international commerce of World Health Organization (WHO)”.

4. Clauses 2, 4 Article 4 shall be amended as follows:

 “2. Regulations on preparation for application:

a) Submission of application in person or by post: The application must be prepared on A4 paper and firmly closed. The application shall have a cover page and a product information sheet that are arranged in the correct order of the table of contents and separated between sections. The separated parts shall be numbered and certified with a seal of the registration establishment or manufacturer in the whole of application. The quality standards, test methods, test sheets of traditional drugs and herbal ingredients shall be signed by the competent person and certified with a seal of the manufacturer.

b) Submission of application in person: The application for marketing authorization shall be prepared in word or pdf file, numbered in each section; arranged in the correct order of the table of contents. The quality standards, test methods, test sheets of traditional drugs and herbal ingredients shall be signed by the competent person and certified with a seal of the manufacturer.”

 “4. The package insert of traditional drugs according to regulations on the method of writing in the package insert of the Ministry of Health shall bear the overlapping seal of the registration establishment. The contents of the indications and the method of use shall include their description in traditional medicine language It is not required to have the package insert for traditional ingredients.”

5. Point c Clause 5 Article 4 shall be amended as follows:

 “c) If the registration establishment is not the manufacturer, the certificate of eligibility to trade herbal ingredients and traditional drugs of the registration establishment shall be a certified true copy or a copy certified with a seal of the manufacturer."

6. Point a Clause 6 Article 4 shall be amended as follows:

 “a) CPP; certificate of eligibility to produce and trade herbal ingredients and traditional drugs issued by the foreign competent state management agency; good manufacturing practices (GMP); license to establish representative office in Vietnam (hereinafter referred to as “legal documents”) shall be authentic copies or certified true copies:

- The authentic copy shall have signature, name of the signer and seal of the competent state management agency of the issuing country. The signature, name, title of signer and seal of the competent state agencies shall be consularly legalized in accordance with the law on consular legalization, except for the legal documents issued by the competent state management agencies of the issuing countries which have signed mutual legal assistance treaties with Vietnam;

- The certified true copy shall be certified by the competent agency or organization of Vietnam in accordance with the law of Vietnam on certification of copy from the original copy. The original copy shall be presented for the purpose of comparison (if necessary);

- If the issued legal document is an electronic document (including documents that fail to have enough signatures, names of the signer and seals of the competent state management agency of the issuing country), the registration establishment must submit one of the following additional documents:

If the legal document fails to have signature and seal of the competent state management agency that issues such document, it is not required to have the signature or seal of the competent state management agency in the document that proves the legal document in accordance with the law of the host country. The results of self-search for legal document from the official website of the agency competent that issues such document shall be certified with a seal and enclosed with the document that provides information on the link for search. The registration establishment shall be responsible to the law for the legality and accuracy of these documents, information and the results of self-search of the establishment.

The legal document shall be consularly legalized according to regulations (original copy or certified true copy).

- The legal documents in the application shall be valid at the time of receipt recorded on the Receipt Form. The legal documents shall be presented in English or Vietnamese. If the legal document is not presented in English or Vietnamese, the registration establishment shall provide the notarized translation in Vietnamese. If the CPP does not specify the validity period, the validity period shall be 24 months from the date of issuance.”

7. Point b Clause 6 Article 4 shall be amended as follows:

 “b) The CPP shall satisfy regulations of point a of this Clause and the following regulations:

- The CPP shall be issued by the competent authority for management of drugs (according to the list of WHO on http://www.who.int), according to the form of the World Health Organization (WHO) applicable to the certification scheme on the quality of pharmaceutical products moving in international commerce.

- If the drug is produced by many different manufacturers, the CPP shall clearly state the name, address and role of each manufacturer;

- If the CPP fails to have information on the drug manufacturer that meets GMP, the registration establishment shall submit the GMP of all the manufacturers.

- The drug subject to circulation in the manufacturing country shall be certified. If the drug is not licensed to circulate in the manufacturing country or has been licensed without circulation in the manufacturing country, the registration establishment shall provide CPP which certifies that the drug has been circulated in reality in one of the countries.

- The information on the CPP shall be consistent with the relevant information in the application”.

8. Clause 8 Article 4 shall be amended as follows:

 “8. Legal documents of the establishments which produce excipients, capsule shells, semi-finished herbal ingredients and herbal ingredients for the production of traditional drugs may be one of the following types of documents:

a) GMP;

b) License for production which certifies that the manufacturer meets GMP;

c) Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP);

d) CPP of excipient, capsule shell or semi-finished herbal ingredients (in case the CPP has information on GMP)

dd) Excipients in the application for marketing authorization of traditional drugs: If the documents specified in one of the points a, b, c, d of this Clause cannot be provided, the manufacturer of the finished or semi-finished drugs shall make self-assessment of the satisfaction of good manufacturing practices of the manufacturer of excipients according to regulations of Point dd Clause 1 Article 3, Point b Clause 3 Article 3 and Point dd Clause 5 Article 20 of Circular No. 35/2018/ TT-BYT dated November 22, 2018 of the Minister of Health on good manufacturing practices for pharmaceutical products and pharmaceutical starting ingredients and self-declaration in the application for registration of traditional drugs on the principles and standards of good manufacturing practices that the excipient-manufacturing establishment meets and commits to take responsibility to law for this declaration according to Form 01/TT issued together with this Circular.”

9. Clause 9 Article 4 shall be amended as follows:

 “9. General regulations on amendments to application for issuance of marketing authorization of traditional drugs and herbal ingredients

a) The time for amendments to application of the registration establishment shall not exceed 90 days from the date of receipt of the written request of the receiving agency. The time for amendments to application of the registration establishment shall fall outside the time limit for consideration of the application. In case of excess of 90 days, the application shall be invalid and the registration establishment shall re-implement the procedure for marketing authorization, except for cases in which it is required to have longer time to amend contents according to the written notification. To be specific:

- Test standards of the quality of finished products.

- Amend GMP/CPP or other legal documents.

- Add the new data on research on the stability according to request of the Director of the Traditional Medicine Administration of Vietnam;

If it is necessary to extend the time according to regulations, the registration establishment may extend the time for amendments to the application without excess of 120 days from the date of receipt of the written request for amendments of the receiving agency.

b) The registration establishment shall be only allowed to amend the same contents at most 02 times. If the registration establishment amends the contents in excess of the time according to regulations, the Traditional Medicine Administration of Vietnam will return the application to the registration establishment for the marketing authorization as the first time.”

10. Article 7 shall be amended as follows:

 “Article 7. Traditional drugs subject to exemption from clinical trials in Vietnam

1. Traditional drugs subject to exemption from clinical trials under recognition of the Ministry of Health shall include the drugs with the origin or formulation in the following cases:

a) Traditional ingredient;

b) Ancient remedy;

c) Home remedy which has been granted the certificate of home remedy according to the provisions of the law with the effects and indications that include their description in traditional medicine language and tested for acute toxicity and semi-chronic toxicity in order to ensure safety and effectiveness.

d) Traditional drugs that have been exempted from clinical trials with change in the dosage form without change in composition, content, indications, effects and the method of use; tested for acute and semi-chronic toxicity to ensure safety and effectiveness;

dd) Dose-adjusted remedy with the documents and data that prove or analyze, justify the dose-adjustment in accordance with the theory of traditional medicine. In case of dose-adjustment, if the ingredients contains herbal ingredients on the list of the toxic herbal ingredients promulgated by the Minister of Health, the acute and semi-chronic toxicity shall be tested to ensure safety and effectiveness;

e) Products of the provincial and equivalent scientific research projects on traditional drugs that have been accepted by the scientific council of the province and decided by the People's Committee of province, or approved by the appropriate Ministry according to applicable regulations. The products have effects, indications that include their description in traditional medicine language and have been tested for acute and semi-chronic toxicity, pharmacological effects in order to ensure safety and effectiveness, except for the cases specified in Article 10 of this Circular;

g) Traditional drugs with indications according to the data on clinical research under the regulations on clinical trials of the Ministry of Health, which have been granted marketing authorization and marketed for more than 10 years without detection of harmful effects and adverse reactions of drugs; or traditional drugs without the data on clinical research which have been granted marketing authorization and marketed for more than 5 years without detection of harmful effects and adverse reactions of drugs or traditional drugs;

h) Dose-adjustment from the remedies that have been granted marketing authorization and marketed on the market for 5 years or more, except for traditional drugs with indications according to the data on clinical research under regulations on clinical trials of the Ministry of Health without detection of harmful effects and adverse reactions of drugs; have the documents and data that prove or analyze and justify the reduction in accordance with the theory of traditional medicine.

2. Traditional drugs that are extended from drugs which have been granted marketing authorizations before the effective date of the Law on Pharmacy No. 105/2016/QH13, except for drugs subject to clinical trials of the Advisory Council for issuance of marketing authorization of traditional drugs and herbal ingredients in case of detection of harmful effects adverse reactions of drugs in circulation.”

11. Article 8 shall be amended as follows:

 “Article 8. Criteria for identification of cases of exemption from some stages of clinical trial of traditional drugs in Vietnam

The traditional drugs shall undergo phase 3 clinical trials without undergoing from phase 1 and phase 2 clinical trials in Vietnam if the drugs meet one of the following criteria:

1. The drugs subject to exemption from clinical trials have change or addition to their indications according to the main effects of the drugs without change in the composition of the drug formulation, dosage or dosage form;

2. The home remedy which has been granted the certificate of home remedy according to the provisions of law fails to satisfy the provisions of Point c, Clause 1, Article 7 of this Circular;

3. The drugs which have been used for treatment at medical facilities with traditional medicine (grade II or higher) have the fixed method of use, dosage, process and dosage form; have effects, indications that include their description in traditional medicine language; have been tested for acute and semi-chronic toxicity, pharmacological effects in order to ensure safety and effectiveness and approved by the Scientific Council of the medical facilities.”

12. Article 10 shall be amended as follows:

 “Article 10. Criteria for identification of traditional drugs subject to the testing in all stages in the following cases: New traditional drugs specified at Point a, Clause 1, Article 89 of the Law on Pharmacy.”

13. Article 11 shall be amended as follows:

"1. Ancient remedy specified in point b, Clause 1 Article 7 of this Circular: Documents that prove the origin of ancient remedy according to regulations of Clause 2 Article 3 of this Circular.

2. Home remedy specified in point c, Clause 1 Article 7 or Clause 2 Article 8 of this Circular:

a) Copy that is certified or sealed by the holder of certificate of home remedy. Submission of the copy sealed by the certificate holder: it is required to have a original copy or a certified true copy for comparison of the application-receiving division;

b) Certified true copy of the result of testing of acute toxicity and semi-chronic toxicity according to regulations.

3. Traditional drugs subject to exemption from clinical trials with change in the dosage form:

a) Document on drug formulation; method of preparation for ingredients; new dosage form;

b) Manufacture process after change from the previous dosage form;

c) Document that proves the origin of the traditional drugs subject to exemption from clinical trials for the purpose of change in the dosage form

4. Traditional drugs subject to exemption from clinical trials which have change or addition to their indications according to the main effects of the drugs without change in the composition of the drug formulation, dosage or dosage form:

a) Document on drug formulation; method of preparation for ingredients; dosage form, dosage;

b) Document that proves or analyzes and justifies the addition of indications according to the main effects of the remedy;

c) Document that proves the origin of the traditional drugs subject to exemption from clinical trials.

5. Dose-adjusted remedy specified in Point dd Clause 1 Article 7 of this Decree;

a) Document that proves the origin of ancient remedy according to regulations of Clause 2 Article 3 of this Circular.

b) Document on drug formulation; method of preparation for ingredients; dosage form, method of use, dosage, indications and contraindications;

c) Document that proves or analyzes, justifies the dose-adjustment in accordance with the theory of traditional medicine

d) Certified true copy of the result of testing of acute toxicity and semi-chronic toxicity according to regulations in case the adjusted ingredient contains herbal ingredients on the list of the toxic herbal ingredients promulgated by the Minister of Health.

6. Drug that is product of scientific research:

a) Certified true copy of the record of acceptance of the scientific research topic;

b) Certified true copy of the result of testing of acute toxicity and semi-chronic toxicity according to regulations.

7. Drugs used for treatment at medical facilities specified in Clause 3 Article 8 of this Circular:

a) Document on drug formulation; method of preparation for ingredients; dosage form, method of use, dosage, indications and contraindications;

b) Certified true copy of the written acceptance of assessment of the safety and effectiveness of the Science and Technology Council of the medical facility.

8. In case of drugs that have been granted marketing authorizations, the proving document is the marketing authorization book.

9. Drug that has been granted marketing authorizations with dose-adjustment, the proving document is the registration number and the document that proves, analyzes or justifies the dose-adjustment in accordance with the theory of traditional medicine.

14. Article 14 shall be amended as follows:

1". Requirements for clinical data for the purpose of assurance about the safety and effectiveness in the marketing application of traditional drugs

a) In case of clinical studies of drugs, the data in the clinical dossiers shall be consistent with the Guidelines for preclinical and clinical research on drugs of the Ministry of Health or other organizations recognized by Vietnam, including: Research guidelines for evaluating the safety and efficacy of herbal medicines of WHO If the research is carried out before the above-mentioned regulations and guidelines for drug research and development, the research data will be considered and accepted for appraisal;

b) Traditional drugs with data cited from the following documents shall be considered as the clinical data in order to assess the safety and effectiveness of the drugs:

- Treatises relevant to the safety and effectiveness of pharmaceutical drugs that are mentioned in the pharmacopoeias of Vietnam or other countries in the world. These treaties shall contain full data on clinical trial;

- Articles about evaluation of the safety and effectiveness of drugs that have been published in journals of the SCI (Science Citation Index) and clinical data gathered from research works published in other medical literature. These articles shall contain full data on clinical trial;

- Reports on assessment of safety and effectiveness of national, ministerial or provincial science and technology projects that have been accepted.

2. The clinical studies of the drug, the data in the clinical dossiers and the technical dossiers that prove the safety and effectiveness shall be consistent with the regulations of the Ministry of Health on good clinical practice.

3. The existing data in the result of clinical trial of the drug can be used to analyze and justify the possible influence of epidemiological, pathological or living conditions in Vietnam on the safety and effectiveness of the drug.”

15. Point a Clause 2 Article 16 shall be amended as follows:

 “a) Copy of certificate of eligibility to trade herbal ingredients and traditional drugs with the scope for trade and production of traditional drugs or herbal ingredients for domestic drug manufacturers.”

16. Point b Clause 3 Article 16 shall be amended as follows:

 “b) The legal documents of the establishment that makes marketing authorization of traditional drugs shall includes one of the following documents:

- Copy of certificate of eligibility to trade herbal ingredients and traditional drugs for the domestic establishment with one of the scope for trade: production, business, export or import of traditional drugs or herbal ingredients;

- License to establish representative office in Vietnam; certificate of eligibility to produce and trade herbal ingredients and traditional drugs issued by the foreign competent state management agency according to regulations for the foreign establishment with one of the scope for trade: production, business, export or import of drugs.”

17. Clause 10 Article 16 shall be amended as follows:

 “10. Copy of legal document of the establishment which produces excipients, capsule shells, semi-finished herbal ingredients and herbal ingredients for the production of traditional drugs according to Clause 8 Article 4 of this Circular.”

18. Clauses 1, 2 Article 17 shall be amended as follows:

 “1. Document on the process of production according to Form No. 02/TT issued together with this Circular shall satisfy the following requirements:

a) Documents on raw ingredients: Describe the process of preliminary processing and processing of ingredients of herbal ingredient in a detailed and complete manner. In case of raw ingredients that are semi-finished herbal ingredients (ingredients in the form of glue, granule, powder), it is required to have the detailed description of the process of production of semi-finished herbal ingredients from ingredients of herbal ingredients (except for semi-finished herbal ingredients which have been granted marketing authorizations);

b) Document on finished drugs shall fully show the following information:

- Formula for smallest package unit: names of ingredients (including herbal ingredients, auxiliary ingredients and excipients); standards of application of ingredients. In case of production from ingredients in the form of glue that have not been standardized in terms of content of active ingredients, the corresponding content of herbal ingredients shall be clearly stated;

- Formula for a batch of production: names of ingredients including main ingredients and excipients; mass or volume of each ingredient;

- Diagram of the process of production: all stages in the production process;

- Description of the process of production: Detailed description of each stage in the production process;

- List of equipment and tools used in the process of production: name of equipment, parameters, capacity, model, purpose of use, status of use, registration number or declaration (if any);

- Control in the process of production: Detailed description of the criteria for inspection and control in the production process.

2. Documents on standards of the quality and methods of testing of drugs shall meet the following requirements:

a) Standards of ingredients:

- Herbal ingredients that fall into the pharmacopoeia: Specify the name of the pharmacopoeia and the year of publication;

- Herbal ingredients that fall outside in the pharmacopoeia: Describe criteria and testing methods in a detailed and complete manner;

- Standards of auxiliary materials in the processing of herbal ingredients: The establishment shall have measures to control the quality of the auxiliary materials. Auxiliary materials with national standards: Write the standard number.

b) Standards of finished drugs: Describe criteria and testing methods in a detailed and complete manner

b) Standards of packaging: Describe criteria and testing methods in a detailed and complete manner

d) Testing reports:

- The traditional drug production establishments which have laboratories under Good Drug Laboratory Practice (GLP) according to the regulations of the Ministry of Health shall self-evaluate the testing standards and methods and submit their own testing reports;

- The traditional drug manufacturing establishments that do not have laboratories under Good Laboratory Practices (GLP) according to the regulations of the Ministry of Health shall appraise the testing standards and methods and submit testing reports of the drug testing facilities that meet GLP or the drug testing service providers that has been issued certificates of eligibility to trade herbal ingredients and traditional drugs

- Quantity of testing reports:

01 testing report on herbal ingredients of the manufacturer of finished drugs. If the herbal ingredients have been supplied by many different manufacturers, it is required to have only 01 testing report of herbal ingredients that is representative);

01 testing report on semi-finished herbal ingredients of the manufacturer of semi-finished herbal ingredients. If the semi-finished herbal ingredients have been supplied by many different manufacturers, it is required to have only 01 testing report that is representative and 01 testing report on semi-finished herbal ingredients of the manufacturer of finished drugs);

01 testing report on finished drugs;

01 testing report on packaging;

Chromatographic images of the qualitative and quantitative tests throughout the testing.

dd) Requirements for stability studies:

Traditional medicine production establishments shall study and have documents that prove the stability, including:

- Stability study outline;

- Stability study data;

- Stability study conclusion;

- The testing reports on finished drugs of the stability monitoring samples shall include 03 samples at the initial time; 03 samples at the time after the shelf life in the long-term condition and 03 samples at the end of the stability study under the condition of the accelerated aging.”

19. Clauses 3, 5 Article 20 shall be amended as follows:

 “3. Traditional drugs that are not subject to clinical trial: Within 06 months from the date of receipt of the application, the receiving agency shall grant written approval or disapproval of issuance of marketing authorizations of traditional drugs. To be specific:

a) Within 15 days from the date of receipt of the application, the receiving agency shall transfer the application to the appraisal expert or unit under decision of the Minister of Health (hereinafter referred to as “appraisers”) in order to review and give opinions according to the list of appraisers established and approved by the Traditional Medicine Administration or the appraisal units;

b) Within 60 days from the date on which the appraisers consider and give their opinions, the receiving agency will transfer the applications for issuance or refusal of issuance of marketing authorizations of drugs and medicinal ingredients or the application for appraisal and counseling to the Office of the Advisory Council for submission to the Advisory Council.

c) Within 15 days from the date on which the Advisory Council gives its opinions, the Minister of Health shall authorize the Director of the Traditional Medicine Administration of Vietnam to issue or refuse to issue marketing authorizations of traditional drugs or request amendments according to the request of the Advisory Council.”

 “5. If the application fails to meet the requirements specified in Articles 15, 16 and 17 of this Circular, within the time limit for consideration of the application, the receiving agency shall promptly provide specific instructions for the registration establishment in order to amend the application until the application meets the requirements. The time and number of times that the registration establishment amends the application shall comply with Clause 9 Article 4 of this Circular.”

20. Clauses 3, 4 Article 21 shall be amended as follows:

 “3. Within 01 month from the date of receipt of the application, the receiving agency shall grant written approval or disapproval of extension of marketing authorizations of traditional drugs. To be specific:

a) Within 05 days from the date of receipt of the application, the receiving agency shall transfer the application to the appraiser;

b) Within 15 days from the date on which the appraiser completes appraisal, the receiving agency shall transfer the applications for issuance or refusal for issuance of marketing authorizations of drugs and medicinal ingredients or the application for appraisal and counseling to the Office of the Advisory Council for submission to the Advisory Council.

c) Within 05 days from the date on which the Advisory Council gives its opinions, the Minister of Health shall authorize the Director of the Traditional Medicine Administration of Vietnam to extend or refuse to extend marketing authorizations of traditional drugs or request amendments according to the request of the Advisory Council.”

4. If the application fails to meet the requirements specified in Article 18 of this Circular, within the time limit for consideration of the application, the receiving agency shall promptly provide specific instructions for the registration establishment in order to amend the application until the application meets the requirements. The time and number of times that the registration establishment amends the application shall comply with Clause 9 Article 4 of this Circular.”

21. Clause 3, 4 and 5 Article 22 shall be amended as follows:

"3. In case of the marketing application of traditional drugs with minor variations as prescribed in Section II.2 Appendix II issued together with this Circular, the establishment can conduct the changed contents right after the date on which the receiving agency issues the receipt certificate to the applicant.

4. In case of marketing application of traditional drugs with major variations as prescribed in Section I, Appendix II and the marketing application of traditional drugs with minor variations in Section II.1 of Appendix II enclosed together with this Circular, within 01 month from the date of receipt of the application, the receiving agency shall grant written approval or disapproval of the changed contents of marketing authorizations of traditional drugs. To be specific:

a) Within 05 days from the date of receipt of the application, the receiving agency shall transfer the application to the appraiser;

b) Within 15 days from the date on which the appraiser completes appraisal, the receiving agency shall transfer the contents of changes in indications, dosages and drug users to the Office of the Advisory Council for issuance of marketing authorizations of drugs and medicinal ingredients for submission to the Advisory Council for approval or disapproval.

c) Within 05 days from the date on which the Advisory Council or the appraiser gives its opinions, the Minister of Health shall authorize the Director of the Traditional Medicine Administration of Vietnam to grant written approval or disapproval of the changed contents of marketing authorizations of traditional drugs.”

5. If the application fails to meet the requirements specified in Article 19 of this Circular, within the time limit for consideration of the application for change, the receiving agency shall promptly provide specific instructions for the registration establishment in order to amend the application until the application meets the requirements. The time and number of times that the registration establishment amends the application shall comply with Clause 9 Article 4 of this Circular.”

22. Clause 7 Article 22 shall be amended as follows:

 “7. The time limit for implementation of the amended contents of marketing authorizations of traditional drugs shall not exceed 6 months from the date on which the Director of the Traditional Medicine Administration promulgates an Official Dispatch on approval for amendments, except for cases under other requests of the Traditional Medicine Administration

23. Clause 8 Article 22 shall be amended as follows:

 “8. In some cases of amendments, the drug registration establishments and manufacturers shall update on labels and instructions for drug use and not submit the application or notification to the Traditional Medicine Administration. To be specific:

a) Carry out labeling and package inserts of drugs and medicinal ingredients according to regulations of Clause 2, Article 35 of the Circular No. 01/2018/TT-BYT dated January 18, 2018 of the Ministry of Health on labeling and package inserts of drugs and medicinal ingredients;

b) Amend the contents of labels and package inserts in accordance with the contents of the written request of the Director of the Traditional Medicine Administration;

c) Other contents

- Change of information on the importers of drugs or medicinal ingredients stated on the labels or package inserts of the drugs;

- Correct spelling mistakes on the labels or package inserts;

- Change the layout of the items in the package insert without change in the approved contents of the package insert;

- Add information on standards of the quality on labels and package inserts according to the application approved by the Director of the Traditional Medicine Administration;

- The amended contents shall comply with the document of the Director of the Traditional Medicine Administration on notification of the results of the appraisal of the application for drugs and medicinal ingredients.”

24. Clause 2 Article 23 shall be amended as follows:

 “2. Applications and procedures for traditional drugs in case of priority given to the reduction in time

a) Traditional drugs that are not subject to clinical trials: within 04 months from the date of receipt of the applications, the receiving agency shall carry out the procedures specified in Clauses 3, 5 and 6, Article 20 of this Circular;

b) Traditional drugs that are subject to clinical trials: within 08 months from the date of receipt of the applications, the receiving agency shall carry out the procedures specified in Clauses 4, 5 and 6 Article 20 of this Circular;

25. Point d Clause 2 Article 26 shall be added as follows:

 “d) Quantity of testing reports:

- 01 testing report on herbal ingredients; If the herbal ingredients have been supplied by many different manufacturers, it is required to have only 01 representative testing report of herbal ingredients);

- 01 testing report on packaging;

26. Clauses 3, 4 Article 29 shall be amended as follows:

 “3. Within 06 months from the date of receipt of the application, the receiving agency shall grant written approval or disapproval of issuance of marketing authorizations of herbal ingredients. To be specific:

a) Within 15 days from the date of receipt of the application, the receiving agency shall transfer the application to the appraiser;

b) Within 60 days from the date on which the appraisers consider and give their opinions, the receiving agency will transfer the applications for issuance or refusal of issuance of marketing authorizations of drugs and medicinal ingredients or the application for appraisal and counseling to the Office of the Advisory Council for submission to the Advisory Council.

c) Within 15 days from the date on which the Advisory Council gives its opinions, the Minister of Health shall authorize the Director of the Traditional Medicine Administration of Vietnam to issue or refuse to issue marketing authorizations of herbal ingredients or request amendments according to the request of the Advisory Council.”

4. If the application fails to meet the requirements specified in Articles 24, 25 and 26 of this Circular, within the time limit for consideration of the application, the receiving agency shall promptly provide specific instructions for the registration establishment in order to amend the applications until the application meets the requirements. The time and number of times that the registration establishment amends the application shall comply with Clause 9 Article 4 of this Circular.”

27. Clauses 3, 4 Article 30 shall be amended as follows:

 “3. Within 03 months from the date of receipt of the application, the receiving agency shall grant written approval or disapproval of extension of marketing authorizations of herbal ingredients. To be specific:

a) Within 05 days from the date of receipt of the application, the receiving agency shall transfer the application to the appraiser;

b) Within 30 days from the date on which the appraisers consider and give their opinions, the receiving agency will transfer the applications for issuance or refusal of issuance of marketing authorizations of drugs and medicinal ingredients or the application for appraisal and counseling to the Office of the Advisory Council for submission to the Advisory Council.

c) Within 15 days from the date on which the Advisory Council gives its opinions, the Minister of Health shall authorize the Director of the Traditional Medicine Administration of Vietnam to extend or refuse to extend marketing authorizations of herbal ingredients or request amendments according to the request of the Advisory Council.”

4. If the application fails to meet the requirements specified in Article 27 of this Circular, within the time limit for consideration of the application, the receiving agency shall promptly provide specific instructions for the registration establishment in order to amend the application until the application meets the requirements. The time and number of times that the registration establishment amends the application shall comply with Clause 9 Article 4 of this Circular.”

28. Clause 3, 4 and 5 Article 31 shall be amended as follows:

"3. In case of the marketing application of herbal ingredients with minor variations as prescribed in Section II.2 Appendix II issued together with this Circular, the establishment can conduct the changed contents right after the date on which the receiving agency grants the receipt certificate to the applicant.

4. In case of marketing application of herbal ingredients with major variations as prescribed in Section I, Appendix II and the marketing application of herbal ingredients with minor variations in Section II.1 of Appendix II enclosed together with this Circular, within 01 month from the date of receipt of the application, the receiving agency shall grant written approval or disapproval of the changed contents of marketing authorizations of herbal ingredients. To be specific:

a) Within 05 days from the date of receipt of the application, the receiving agency shall transfer the application to the appraiser;

b) Within 15 days from the date on which the appraiser gives its opinions, the Minister of Health shall authorize the Director of the Traditional Medicine Administration of Vietnam to grant written approval or disapproval of the changed contents of marketing authorizations of herbal ingredients for the applications that meet requirements.”

5. If the application fails to meet the requirements specified in Article 28 of this Circular, within the time limit for consideration of the application for change, the receiving agency shall promptly provide specific instructions for the registration establishment in order to amend the application until the application meets the requirements. The time and number of times that the registration establishment amends the application shall comply with Clause 9 Article 4 of this Circular.”

29. Clause 7 Article 31 shall be amended as follows:

 “7. The time limit for implementation of the amended contents of marketing authorizations of herbal ingredients shall not exceed 6 months from the date on which the Director of the Traditional Medicine Administration promulgates an Official Dispatch on approval for amendments, except for cases under other requests of the Traditional Medicine Administration

30. Clause 8 Article 31 shall be amended as follows:

 “8. In some cases of amendments, the drug registration establishments and manufacturers shall update on labels and not submit the application or notification to the Traditional Medicine Administration. To be specific:

a) Carry out labeling of herbal ingredients according to regulations of Clause 2, Article 35 of the Circular No. 01/2018/TT-BYT dated January 18, 2018 of the Ministry of Health on labeling and package inserts of drugs and medicinal ingredients;

b) Amend the contents of labels in accordance with the contents of the written request of the Director of the Traditional Medicine Administration;

c) Other contents

- Change of information on the importers of herbal ingredients stated on the labels;

- Correct spelling errors on the labels;

- Add information on standards of the quality on labels according to the application approved by the Director of the Traditional Medicine Administration;

- The amended contents shall comply with the document of the Traditional Medicine Administration on notification of the results of the appraisal of the application for drugs and medicinal ingredients.”

31. Point c Clause 1 Article 32 shall be added as follows:

 “c) Herbal ingredients used to produce drugs shall meet urgent needs for national defense and security, disease prevention and control, natural disaster recovery and special treatment.

32. Clause 2 Article 32 shall be amended as follows:

 “2. Applications and procedures for herbal ingredients in case of priority given to the reduction in time

a) Within 04 months from the date of receipt of the applications, the receiving agency shall carry out the procedures specified in Clauses 3, 5 and 6, Article 20 of this Circular for herbal ingredients that are prioritized for consideration of reduction in the time for issuance of marketing authorization according to regulations of Points a, b Clause 1 of this Article.

b) Within 01 month from the date of receipt of the applications, the receiving agency shall carry out the procedures specified in Clauses 3, 4 and 5, Article 29 of this Circular for herbal ingredients that are prioritized for consideration of reduction in the time for issuance of marketing authorization according to regulations of Point c Clause 1 of this Article.

33. Clause 1 Article 36 shall be amended as follows:

 “1. The Minister of Health establishes an Advisory Council for the issuance of marketing authorization of traditional drugs and herbal ingredients. The Advisory Council includes: the President of the Council; Vice President(s) of the Council; Council Members and Council Office that is Working Assistance Standing Department.”

34. Clause 4 Article 37 shall be amended as follows:

 “4. The Traditional Medicine Administration develops and promulgates regulations on criteria for selection, organization and operation of the appraisers; signs a contract with the appraiser or a unit the participates in the appraisal of application; organizes training courses, training for the appraisers; conduct assessment of the professional capacity and compliance with regulations in order to adjust and add the appropriate appraisers.”

35. Clause 5 Article 37 shall be amended as follows:

 “5. The funding for the appraisal of application shall comply with regulations of law.

36. Appendix II attached to this Circular shall be amended as follows:

Article 2: Entry into force

This Circular comes into force as of February 15, 2022.

Article 3. Transition

The applications submitted before the effective date of this Circular shall continue to comply with the regulations of Circular No. 21/2018/TT-BYT dated September 12, 2018 of the Minister of Health on marketing authorization of traditional drugs and herbal ingredients.

Article 4. Terms of reference

If legislative documents referred to herein are superseded or amended, the new ones shall apply.

Article 5. Responsibility of implementation

Chiefs of the Ministry Offices, Chief Inspectors of Ministries, Director of Traditional Medicine Administration, Directors or Heads of units affiliated to Ministry of Health, Departments of Health of provinces, pharmaceutical business establishments and other relevant agencies, organizations and individuals shall be responsible for the implementation of this Circular../.

Difficulties that arise during implementation of this Circular should be reported to Traditional Medicine Administration, Ministry of Health for consideration./.