Circular No. 39/2021/TT-BYT amends and supplements some articles of Circular No. 21/2018/TT-BYT dated September 12, 2018, of the Minister of Health on the registration for circulation of traditional medicine and medicinal materials.

CIRCULAR

AMENDMENTS AND SUPPLEMENTS TO SOME ARTICLES OF CIRCULAR NO. 21/2018/TT-BYT DATED SEPTEMBER 12, 2018, ISSUED BY THE MINISTER OF HEALTH ON THE REGISTRATION FOR CIRCULATION OF TRADITIONAL MEDICINES AND DRUG MATERIALS

Pursuant to the Medicine Law No. 105/2016/QH13 dated April 6, 2016;6/QH13 April 6, 2016;

Pursuant to the Decree No. 54/2017/NĐ-CP dated May 8, 2017 of the Government detailing some provisions and measures for implementing the Medicine Law;

Pursuant to the Decree No. 155/2018/NĐ-CP dated November 12, 2018 of the Government amending and supplementing certain regulations related to investment and business conditions within the scope of management of the Ministry of Health;

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

At the proposal of the Director of the Department of Traditional Medicine and Drugs,

The Minister of Health issues this Circular amending and supplementing some articles of Circular No. 21/2018/TT-BYT dated September 12, 2018, issued by the Minister of Health on the registration for circulation of traditional medicines and drug materials.

Article 1. Amending and supplementing some articles of Circular No. 21/2018/TT-BYT dated September 12, 2018, issued by the Minister of Health on the registration for circulation of traditional medicines and drug materials

1. Amending and supplementing Article 1 is as follows:

"This Circular provides detailed provisions on the following matters:

1. Cases where the Ministry of Health recognizes traditional medicines exempt from clinical trials; criteria for determining cases exempted from certain phases of clinical trials, required to conduct phase 4 clinical trials, required to conduct full clinical trials, and requirements for clinical data to ensure safety and efficacy in the registration dossier for circulation of traditional medicines.

2. Documents, procedures for issuing, extending, changing, and supplementing the registration certificate for circulation of traditional medicines and drug materials.

3. Revocation of the registration certificate for circulation of traditional medicines and drug materials.

4. Advisory Council for issuing the registration certificate for circulation of traditional medicines and drug materials (hereinafter referred to as the Advisory Council) and experts reviewing the registration dossier for circulation of traditional medicines and drug materials."

2. Amend Clause 2 and Clause 3 of Article 3 as follows:

“2. Ancient prescription (ancient formula) means prescriptions recorded in books on traditional medicine or prescriptions recorded in pharmacopoeias of other countries collected and promulgated by the Ministry of Health in the List of Ancient Prescriptions.

3. Modified ancient prescription means an ancient prescription with an increase or decrease in the number of medicinal ingredients or the dosage of each ingredient to enhance therapeutic effects, reduce toxicity of the prescription suitable for diseases or syndromes according to the theory of traditional medicine."

3. Supplement Clause 6, Clause 7, and Clause 8 Article 3 as follows:

“6. Major changes are significant changes that clearly and directly affect the quality, safety, and efficacy of traditional medicines and drug materials as specified in Appendix II attached hereto.

7. Minor changes are changes that do not affect or have very little impact on the efficacy, quality, and safety of traditional medicines and drug materials as specified in Appendix II attached hereto.

8. Certificate of Pharmaceutical Product (CPP) is a certificate issued under the WHO Quality Certification System for pharmaceutical products circulating in international trade."

4. Amend and supplement Clause 2 and Clause 4 Article 4 as follows:

"2. Provisions on preparing the dossier:

a) In case of submitting the dossier directly or through postal service: The registration dossier must be prepared on A4 paper size, securely bound. The dossier must have a cover page, product information sheet, arranged in accordance with the table of contents, separated by sections; each section must be numbered and stamped by the registering entity or the manufacturing entity throughout the entire dossier; specifically, quality standards, testing methods, and test reports for traditional medicines and drug materials must bear the signature of the authorized person and the stamp of the manufacturer.

b) In case of submitting the dossier online: The registration dossier must be prepared in Word or PDF format, numbered by sections; arranged in accordance with the table of contents; specifically, quality standards, testing methods, and test reports for traditional medicines and drug materials must bear the signature of the authorized person and the stamp of the manufacturer."

"4. The instructions for use of traditional medicines shall comply with the regulations on the format of drug instructions issued by the Ministry of Health, stamped with the seal of the registering entity. The indication and usage must clearly reflect the traditional medical syndrome. Instructions for use are not required for individual traditional medicinal ingredients."

5. Amend Point c Clause 5 of Article 4 as follows:

"c) In case the registering entity is different from the manufacturing entity, the business license for pharmaceuticals of the registering entity must be a certified copy or a copy self-stamped by the manufacturing entity."

6. Amend and supplement Point a Clause 6 of Article 4 as follows:

"a) Certificate of Pharmaceutical Product (CPP); Pharmaceutical Production and Business License issued by competent authorities of foreign countries; Good Manufacturing Practice (GMP) Certificate; Representative Office Establishment Permit in Vietnam (collectively referred to as legal documents) must be original or certified copies:

- Originals must be fully signed, named, and stamped by the competent authority of the issuing country; signatures, names, and positions of the signatories and stamps of the competent authority must be legalized according to the laws on legalization of foreign public documents, except in cases where the legal documents are issued by competent authorities of countries that have concluded Mutual Legal Assistance Treaties with Vietnam;

- Certified copies must be certified by competent authorities in Vietnam according to Vietnamese laws on certification of copies from originals. In necessary cases, the original must be presented for verification;

- In case the legal document is an electronic version, including cases without signatures, stamps of the competent authority of the issuing country, the registering entity must submit one of the following documents:

Documentation proving that the legal document does not require signatures or stamps of the competent authority according to the laws of the issuing country (if the legal document does not have signatures or stamps of the competent authority); results of self-checking the legal document from the official website of the issuing authority, accompanied by a letter providing the link for checking, stamped by the entity. The registering entity is responsible for the legality and accuracy of these documents, information, and self-checking results.

Legal documents must be legalized according to the regulations (original or certified copy).

- Legal documents in the dossier must be valid at the time of receipt as recorded on the Receipt Form and must be presented in English or Vietnamese. In cases where legal documents are not in English or Vietnamese, the registration entity must provide a certified translation in Vietnamese. If the Certificate of Pharmaceutical Product (CPP) does not indicate its validity period, the validity period shall be considered to be 24 months from the date of issuance.

7. Amend and supplement point b, Clause 6, Article 4 as follows:

“b) The CPP must comply with the provisions set out in point a of this clause and meet the following requirements:

- Issued and granted by the competent drug regulatory authority (according to the list on the WHO website http://www.who.int) in accordance with the World Health Organization (WHO) model applicable to the Quality Assurance System for products circulating in international trade;

- In cases where the medicine is produced by multiple production facilities, the CPP must clearly state the name, address, and role of each production facility;

- Where the CPP does not contain information about the production facility meeting Good Manufacturing Practice (GMP), the registration entity must submit a GMP certificate for all participating production facilities;

- There must be confirmation that the medicine is permitted to circulate in the country of manufacture. In cases where the medicine is not authorized to circulate in the country of manufacture or has been authorized but is not actually circulating there, the registration entity must provide a CPP with confirmation that the medicine is circulating in one of the countries where it is actually circulating;

- The information on the CPP must be consistent with relevant information in the medicine registration dossier.”

8. Supplement Clause 8 Article 4 as follows:

“8. Legal documents of the production facility for excipients, capsules, semi-finished herbal products, and herbs for producing traditional medicines may be one of the following types of documents:

a) GMP certificate;

b) Production permit with confirmation that the production facility meets GMP requirements;

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

d) CPP of excipients, capsules, semi-finished herbal products if the CPP contains GMP information;

đ) For excipients in the traditional medicine registration dossier: In cases where the documents specified in points a, b, c, and d of this clause cannot be provided, the finished product manufacturing facility or semi-finished product manufacturing facility must conduct self-assessment of the compliance with good manufacturing practices of the excipient manufacturing facility according to point đ of Clause 1, Article 3, point b of Clause 3, Article 3, and point đ of Clause 5, Article 20 of Circular No. 35/2018/TT-BYT dated November 22, 2018 issued by the Minister of Health on Good Manufacturing Practices for Medicines and Active Pharmaceutical Ingredients and Self-Declaration, and declare in the registration dossier the principles and standards of good manufacturing practices that the excipient manufacturing facility complies with and commit to legal responsibility for such declaration according to Model 01/TT attached to this Circular.”

9. Supplement Clause 9 Article 4 as follows:

“9. General provisions on amending and supplementing the application dossier for obtaining a circulation permit

a) The time limit for the registration entity to amend and supplement the dossier shall not exceed 90 days from the date of receipt of the request from the receiving agency. The time taken to amend and supplement the dossier shall not be included in the review period. If the deadline of 90 days is exceeded, the registration dossier will lose its validity and the entity must reapply for registration, except in cases where the notification letter requires amendments and supplements that need a longer time to implement, such as:

- Quality control testing of finished products.

- Supplementing GMP/CPP or other legal documents.

- Supplementing new stability study data as required by the Traditional Medicine Management Department.

In cases requiring an extension of time as stipulated above, the entity may extend the amendment and supplementation period up to 120 days from the date of receipt of the request for amendment and supplementation from the receiving agency.

b) The entity is only allowed to amend and supplement the dossier no more than twice for the same requirement. If the number of amendments and supplements exceeds the aforementioned limit, the Traditional Medicine Management Department will return the dossier to the entity to reapply for registration as if it were the first time.”

10. Amend and supplement Article 7 as follows:

“Article 7. Cases where traditional medicines are exempted from clinical trials in Vietnam

1. Traditional medicines recognized by the Ministry of Health as exempted from clinical trials include those belonging to the following categories:

a) Traditional medicinal ingredients;

b) Ancient prescriptions;

c) Family-inherited prescriptions that have been granted a certificate of family-inherited prescription in accordance with the law, with clear indications and therapeutic effects reflecting traditional medical conditions, and have undergone acute and subchronic toxicity tests to ensure safety and efficacy;

d) Traditional medicines that have been exempted from clinical trials and have changed dosage forms without altering their components, concentrations, indications, effects, or routes of administration, and have undergone acute and subchronic toxicity tests to ensure safety and efficacy;

đ) Modified ancient prescriptions with evidence or data analysis demonstrating the appropriateness of modifications based on traditional medical theory. In cases where modifications involve herbal ingredients listed in the directory of toxic herbs issued by the Minister of Health, acute and subchronic toxicity tests must be conducted to ensure safety and efficacy;

e) Products resulting from scientific research projects at provincial level or higher on traditional medicines, approved by the Scientific Council of the province/city and decided by the Provincial People's Committee or reviewed and approved by the competent ministry according to current regulations, with clear indications and therapeutic effects reflecting traditional medical conditions, and have undergone acute and subchronic toxicity tests and pharmacological studies to ensure safety and efficacy, except as provided in Article 10 of this Circular;

g) Traditional medicines with indications based on clinical trial data in accordance with the Ministry of Health's regulations on clinical trials, which have been granted a circulation permit and have been circulating for over 10 years without additional adverse reactions or harmful effects being discovered, or traditional medicines without clinical trial data that have been granted a circulation permit and have been circulating for over 5 years without additional adverse reactions or harmful effects being discovered;

h) Adjustments from traditional medicine prescriptions that have been granted registration certificates and have been circulating on the market for five years or more, except for traditional medicines based on clinical trial data according to the Ministry of Health's regulations on clinical trials, without discovering new adverse effects and harmful reactions; there must be documentation, data proving or analyzing and explaining the adjustments in accordance with the theory of traditional medicine.

2. Traditional medicines extended from those that were granted registration certificates before the Pharmaceutical Law No. 105/2016/QH13 took effect, except for medicines proposed to undergo clinical trials by the Advisory Council for Registration Certificates of Traditional Medicines and Herbal Drugs when additional adverse effects and harmful reactions are discovered during circulation.

11. Amended Article 8 as follows:

"Article 8. Criteria for determining cases exempted from certain phases of clinical trials for traditional medicines in Vietnam

Criteria for determining medicines exempted from Phase 1 and Phase 2 clinical trials but required to continue Phase 3 clinical trials in Vietnam if they meet any of the following criteria:

1. Medicines belonging to cases exempted from clinical trials but have changes or additions to indications based on the main effects of the prescription without changing the formula components, dosage, or preparation form;

2. Inherited prescriptions that have been granted certificates of inherited prescriptions according to the law, but do not meet the provisions of point c, Clause 1, Circular 7, but do not comply with the provisions of point c, Clause 1, or Clause 2, Article 8 of this Circular;

3. Medicines that have been used for treatment at medical facilities practicing traditional medicine of Class II or higher: having fixed routes of administration, dosages, procedures, and preparation forms; their effects and indications clearly reflect traditional medical conditions, have undergone acute and subchronic toxicity tests and pharmacological actions to ensure safety and efficacy, and have been approved by the Scientific Council of the medical facility."

12. Amend Article 10 is as follows:

"Article 10. Criteria for determining traditional medicines that must undergo all phases of clinical trials in the following cases: New traditional medicines prescribed in point a, Clause 1, Article 89 of the Pharmaceutical Law."

13. Amended and supplemented Article 11 is as follows:

"1. Ancient formulas prescribed in point b, Clause 1, Article 7 of this Circular: Documentation proving the origin and source of the ancient formula according to Clause 2, Article 3 of this Circular.

2. For inherited prescriptions prescribed in point c, Clause 1, Article 7 or Clause 2, Article 8 of this Circular:

a) A certified copy or stamped copy of the certificate of the inherited prescription. If a stamped copy is submitted, the original or a certified copy must be provided for comparison by the file receiving department;

b) A certified copy of the results of acute and subchronic toxicity tests according to the regulations.

3. For traditional medicines that have been exempted from clinical trials and have changed the preparation form:

a) Documentation about the drug formula; methods of preparing each component; new preparation form;

b) Production process after changing from the previous preparation form;

c) Documentation proving the origin and source of the traditional medicine exempted from clinical trials for use in changing the preparation form.

4. For traditional medicines that have been exempted from clinical trials but have changes or additions to indications based on the main effects of the prescription without changing the formula components, dosage, or preparation form:

a) Documentation about the drug formula; methods of preparing each component; preparation form, dosage;

b) Documentation proving or analyzing and explaining the addition of indications based on the main effects of the prescription;

c) Documentation proving the origin and source of the traditional medicine exempted from clinical trials.

5. For adjusted ancient formulas prescribed in point d, Clause 1, Article 7 of this Circular:

a) Documentation proving the origin and source of the ancient formula according to Clause 2, Article 3 of this Circular;

b) Documentation about the drug formula; methods of preparing each component; drug form; method of use, route of administration; dosage; indications and contraindications;

c) Documentation proving or analyzing and explaining the adjustment in accordance with the theory of traditional medicine;

d) A certified copy of the results of acute and subchronic toxicity tests according to the regulations if the adjusted components belong to the list of toxic herbs issued by the Minister of Health.

6. For medicines that are products of scientific research projects:

a) A certified copy of the acceptance report of the scientific research project;

b) A certified copy of the results of acute and subchronic toxicity tests according to the regulations.

7. For medicines used for treatment at medical facilities prescribed in Clause 3, Article 8 of this Circular:

a) Documentation about the drug formula; methods of preparing each component; preparation form; method of use, route of administration; dosage; indications and contraindications;

b) A certified copy of the acceptance report of the safety and efficacy evaluation by the Scientific and Technological Council of the medical facility.

8. For medicines that have been granted a Registration Certificate, the supporting documentation is the registration record.

9. For medicines that have been granted a Registration Certificate and have been adjusted, the supporting documentation includes the registration record and documentation proving or analyzing and explaining the adjustment in accordance with the theory of traditional medicine.

14. Amended and supplemented Article 14 is as follows:

"1. Requirements for clinical data to ensure safety and efficacy in the registration dossier for traditional medicines

a) Clinical studies of the medicine, data in the clinical dossier must be consistent with the Ministry of Health's guidelines for preclinical and clinical drug research or other organizations recognized by Vietnam, including: WHO Research Guidelines for Evaluating the Safety and Efficacy of Herbal Medicines. In cases where the research was conducted before the issuance of these guidelines and regulations on drug development, the data from such research will be considered for review;

b) Traditional medicines with data extracted from the following sources are accepted as clinical data for assessing the safety and efficacy of the medicine:

- Relevant monographs related to the safety and efficacy of the medicine mentioned in the national or international pharmacopoeias and pharmaceutical compendiums. These monographs must include complete clinical trial data;

- Articles reviewing the safety and efficacy of drugs published in journals listed in the SCI (Science Citation Index) - Scientific citation index and clinical data collected from other peer-reviewed publications. These articles must contain complete data on clinical trials.

- Reports evaluating the safety and efficacy of national-level scientific and technological projects that have been accepted upon completion.

2. Clinical studies of drugs, clinical data, and technical files to demonstrate safety and efficacy must comply with the Good Clinical Practice (GCP) regulations set forth by the Ministry of Health for drug clinical trials.

3. Data already available in the results of drug clinical trial studies may be used for analysis and pharmacological interpretation regarding the potential impact of epidemiological, medical, or living conditions in Vietnam on the safety and efficacy of the drug.

15. Amend point a, Clause 2, Article 16 as follows:

“a) A copy of the Certificate of Business Registration for pharmaceuticals with a scope of business including production of traditional medicine or herbal drugs for domestic manufacturing facilities.”

16. Amend point b, Clause 3, Article 16 as follows:

“b) Legal documents of the entity registering the circulation of traditional medicine, including one of the following documents:

- A copy of the Certificate of Business Registration for pharmaceuticals for domestic entities with a scope of business including production, wholesale, export, or import of traditional medicine or herbal drugs;

- A Representative Office Establishment Permit and a Pharmaceutical Production and Trading Permit issued by the competent authority of the foreign country according to regulations for foreign entities with a scope of business including production, wholesale, export, or import of traditional medicine.”

17. Add Clause 10 Article 16 as follows:

“10. A copy of the legal documents of the facility producing excipients, gelatin capsules, semi-finished herbal products, and herbs for the production of traditional medicine as stipulated in Clause 8, Article 4 of this Circular.”

18. Amend and supplement Clause 1 and Clause 2 of Article 17 as follows:

“1. Documentation on the production process according to Model No. 02/TT attached hereto and meeting the following requirements:

a) Documentation on raw materials: Detailed description of the processing and manufacturing processes of herbal raw materials. If the raw material is a semi-finished herbal product (extract, powder, granules), it must detail the production process of the semi-finished herbal product from the herbal raw material (except when the semi-finished herbal product has already been registered for circulation).

b) Documentation on finished products must include the following information:

- Formula for the smallest unit of packaging: name of raw materials, including herbal components, excipients, and excipients; applicable standards for raw materials; if produced from unstandardized herbal extracts, the corresponding amount of herbal material must be clearly stated;

- Formula for a batch or lot: name of raw materials including main components and excipients; quantity or volume of each raw material;

- Flowchart of the production process including all stages of production;

- Description of the production process: detailed description of each stage of the production process;

- List of equipment and tools used in the production process: name of equipment, specifications, capacity, type of machine, purpose, usage status, registration number or announcement (if any);

- Control during production: Detailed description of inspection and control criteria during production.

2. Documentation on quality standards and testing methods for drugs must meet the following requirements:

a) Raw material standards:

- For raw materials included in the Pharmacopoeia: specify the name of the Pharmacopoeia and year of publication;

- For raw materials not included in the Pharmacopoeia: provide a detailed description of the criteria and testing methods;

- Standards for excipients during herbal processing: The facility must have measures to control the quality of excipients. For excipients with national standards, the standard code should be specified.

b) Finished product standards: Provide a detailed description of the criteria and testing methods for finished products;

c) Packaging material standards: Provide a detailed description of the criteria and testing methods;

d) Test reports:

- Traditional medicine manufacturing facilities with laboratories certified under Good Laboratory Practice (GLP) by the Ministry of Health shall self-assess standards and testing methods and submit their own test reports;

- Traditional medicine manufacturing facilities without laboratories certified under GLP by the Ministry of Health must assess standards and testing methods and submit test reports from state laboratories certified under GLP or commercial testing service providers holding a Certificate of Business Registration for Pharmaceuticals;

- Number of test reports as follows:

One test report for herbal raw materials from the manufacturer of finished products (in cases where herbal raw materials are supplied by multiple manufacturers, only one representative test report is required);

One test report for semi-finished herbal products from the manufacturer of semi-finished herbal products (in cases where semi-finished herbal products are supplied by multiple manufacturers, only one representative test report is required) and one test report for semi-finished herbal products from the manufacturer of finished products;

One test report for finished products;

One test report for packaging materials;

Chromatograms of qualitative and quantitative tests conducted during testing.

e) Requirements for stability research:

Traditional medicine manufacturing facilities must conduct stability research and provide documentation proving stability, including:

- Research plan for stability;

- Stability research data;

- Conclusion of stability research;

- Test reports for finished products of samples monitored for stability, including: three initial samples; three samples at the end of the shelf life under long-term conditions and three samples at the end of accelerated aging study.”

19. Amend and supplement Clause 3 and Clause 5 of Article 20 as follows:

"3. For traditional medicines that do not require clinical trials, within six months from the date of receiving all necessary documents, the agency receiving the documents shall issue a written agreement or disagreement to grant the registration certificate for circulation of traditional medicine, specifically as follows:"

"a) Within fifteen days from the date of receiving all necessary documents, the agency receiving the documents shall transfer the documents to the experts for review or units designated by the Minister of Health (hereinafter referred to as the experts for review) to organize examination and provide opinions based on the list of experts for review established and approved by the Traditional Medicine Management Department or the reviewing units;"

"b) Within sixty days from the date the experts for review examine and provide opinions, the agency receiving the documents shall transfer the documents to the Office of the Advisory Council for issuing the registration certificate for medicines and raw materials for medicines for applications requesting issuance, non-issuance, or applications requesting review and advisory opinions to be submitted to the Advisory Council;"

"c) Within fifteen days from the date the Advisory Council provides opinions, the Minister of Health shall authorize the Director of the Traditional Medicine and Pharmaceutical Management Department to issue or not issue the registration certificate for circulation of traditional medicines or request supplements according to the Advisory Council's recommendations."

"5. In cases where the documents do not meet the requirements stipulated in Articles 15, 16, and 17 of this Circular, during the period of examining the application documents, the agency receiving the documents must promptly issue specific guidance documents for the applicant to modify and supplement the documents until they meet the requirements. The time and number of times the applicant modifies and supplements the documents according to Clause 9 of Article 4 of this Circular."

20. Amend and supplement "Clause 3 and Clause 4 of Article 21 as follows:"

"3. Within one month from the date of receiving all necessary documents, the agency receiving the documents shall issue a written agreement or disagreement to grant the extension of the registration certificate for circulation of traditional medicines, specifically as follows:"

"a) Within five days from the date of receiving all necessary documents, the agency receiving the documents shall transfer the documents to the experts for review;"

"b) Within fifteen days from the date the experts for review complete their work, the agency receiving the documents shall transfer the documents to the Office of the Advisory Council for issuing the registration certificate for medicines and raw materials for medicines for applications requesting issuance, non-issuance, or applications requesting review and advisory opinions to be submitted to the Advisory Council;"

"c) Within five days from the date the Advisory Council provides opinions, the Minister of Health shall authorize the Director of the Traditional Medicine and Pharmaceutical Management Department to issue or not issue the extension of the registration certificate for circulation of traditional medicines or request modifications and supplements according to the Advisory Council's recommendations."

"4. In cases where the documents do not meet the requirements stipulated in Article 18 of this Circular, during the period of examining the application documents, the agency receiving the documents must promptly issue specific guidance documents for the applicant to modify and supplement the documents until they meet the requirements. The time and number of times the applicant modifies and supplements the documents according to Clause 9 of Article 4 of this Circular."

21. Amend and supplement "Clause 3, Clause 4, and Clause 5 of Article 22 as follows:"

"3. For registration documents for circulation of traditional medicines with minor changes as prescribed in Section II.2 of Appendix II issued together with this Circular, the applicant may implement the changes and supplements immediately after the agency receiving the documents issues the receipt to the applicant;"

"4. For registration documents for circulation of traditional medicines with major changes as prescribed in Section I of Appendix II and registration documents for circulation of traditional medicines with minor changes as prescribed in Section II.1 of Appendix II issued together with this Circular, within one month from the date of receiving all necessary documents, the agency receiving the documents shall issue a written agreement or disagreement with the content of changes and supplements to the registration certificate for circulation of traditional medicines, specifically as follows:"

"a) Within five days from the date of receiving all necessary documents, the agency receiving the documents shall transfer the documents to the experts for review;"

"b) Within fifteen days from the date the experts for review complete their work, the agency receiving the documents shall transfer the documents to the Office of the Advisory Council for issuing the registration certificate for medicines and raw materials for medicines for changes regarding indications, dosage, and target users to be submitted to the Advisory Council for approval or disapproval;"

"c) Within five days from the date the Advisory Council or the experts for review provide opinions, the Minister of Health shall authorize the Director of the Traditional Medicine and Pharmaceutical Management Department to issue a written agreement or disagreement with the content of changes and supplements to the registration certificate for circulation of traditional medicines;"

"5. In cases where the documents do not meet the requirements stipulated in Article 19 of this Circular, during the period of examining the application documents for changes and supplements, the agency receiving the documents must promptly issue specific guidance documents for the applicant to modify and supplement the documents until they meet the requirements. The time and number of times the applicant modifies and supplements the documents according to Clause 9 of Article 4 of this Circular."

"22. Supplement Clause 7" Article 22 as follows:

"7. The deadline for implementing changes and supplements to the registration certificate for circulation of traditional medicines shall not exceed six months from the date the Director of the Traditional Medicine and Pharmaceutical Management Department signs and issues the approval letter for changes and supplements, except in cases where there are other requirements from the Traditional Medicine and Pharmaceutical Management Department."

"23. Supplement Clause 8" Article 22 as follows:

"8. Some cases of changes and supplements, the applicant for medicines and the manufacturer of medicines can update on the label, instructions for use of medicines without having to submit documents or notify the Traditional Medicine and Pharmaceutical Management Department, including the following cases:"

"a) Implementing the labeling of medicines, raw materials for medicines, and instructions for use of medicines as prescribed in Clause 2 of Article 35 of Circular No. 01/2018/TT-BYT dated January 18, 2018, of the Ministry of Health on labeling of medicines, raw materials for medicines, and the leaflet of instructions for use of medicines;"

"b) Implementing changes and supplements to the content of labels and instructions for use of medicines according to the content in the written request of the Director of the Traditional Medicine and Pharmaceutical Management Department;"

"c) Other contents:"

"- Changing information about the importer of medicines and raw materials for medicines on the label or leaflet of instructions for use of medicines;"

"- Correcting typographical errors on the label or leaflet of instructions for use of medicines;"

"- Changing the layout of sections in the leaflet of instructions for use of medicines without changing the content of the already approved leaflet of instructions for use of medicines;"

"- Supplementing quality standards information on the label and instructions for use of medicines according to the documents already approved by the Director of the Traditional Medicine and Pharmaceutical Management Department;"

- The contents of amendments and supplements according to the text of the Director of the Traditional Medicine Management Department regarding the notification of the results of the examination of drug registration files.

24. Amend and supplement Clause 2 of Article 23 as follows:

“2. Documents and procedures for traditional medicines under priority cases for shortened timeframes:

a) For traditional medicines that do not require clinical trials, within four months from the date of receipt of complete files, the receiving agency shall carry out the procedures as prescribed in Clause 3, Clause 5, and Clause 6 of this Circular;

b) For traditional medicines that require clinical trials, within eight months from the date of receipt of complete files, the receiving agency shall carry out the procedures as prescribed in Clause 4, Clause 5, and Clause 6 of this Circular.”

25. Supplement Point d Clause 2 of Article 26 as follows:

“d) The number of Test Reports as follows:

- One Test Report on medicinal materials. In case medicinal materials are supplied by different manufacturers, only one representative Test Report on medicinal materials needs to be provided.

- One Test Report on packaging material.”

26. Amend and supplement Clause 3 and Clause 4 of Article 29 as follows:

“3. Within six months from the date of receipt of complete files, the file receiving agency shall issue a document agreeing or disagreeing with the issuance of the drug circulation registration certificate, specifically as follows:

a) Within fifteen days from the date of receipt of complete files, the receiving agency shall transfer the file to the expert for review;

b) Within sixty days from the date the experts review and give opinions, the receiving agency shall transfer the registration files requesting issuance, non-issuance, or requesting further review and advisory opinions to the Drug Registration Advisory Council Office;

c) Within fifteen days from the date the Advisory Council gives its opinion, the Minister of Health authorizes the Director of the Traditional Medicine Management Department to issue, not issue the drug circulation registration certificate or request modifications and supplements according to the Advisory Council's recommendations.

4. In cases where the file does not meet the requirements stipulated in Articles 24, 25, and 26 of this Circular, during the file examination period, the receiving agency must promptly provide specific guidance for the registering entity to modify and supplement the file until it meets the requirements. The time and number of times the registering entity modifies and supplements the file according to Clause 9 of Article 4 of this Circular.”

27. Amend and supplement Clause 3 and Clause 4 of Article 30 as follows:

“3. Within three months from the date of receipt of complete files, the file receiving agency shall issue a document agreeing or disagreeing with the extension of the drug circulation registration certificate, specifically as follows:

"a) Within five days from the date of receiving all necessary documents, the agency receiving the documents shall transfer the documents to the experts for review;"

b) Within thirty days from the date the experts review and give opinions, the receiving agency shall transfer the registration files requesting issuance, non-issuance, or requesting further review and advisory opinions to the Drug Registration Advisory Council Office;

c) Within fifteen days from the date the Advisory Council gives its opinion, the Minister of Health authorizes the Director of the Traditional Medicine Management Department to issue, not issue the extension of the drug circulation registration certificate or request modifications and supplements according to the Advisory Council's recommendations.

4. In cases where the file does not meet the requirements stipulated in Article 27 of this Circular, during the file examination period, the receiving agency must promptly provide specific guidance for the registering entity to modify and supplement the file until it meets the requirements. The time and number of times the registering entity modifies and supplements the file according to Clause 9 of Article 4 of this Circular.”

28. Amend and supplement Clause 3, Clause 4, and Clause 5 of Article 31 as follows:

“3. For drug circulation registration files with minor changes as prescribed in Section II.2 of Appendix II issued together with this Circular, the entity may implement the changes and supplements immediately after the file receiving agency issues the Receipt Acknowledgment to the registering entity.

4. For drug circulation registration files with major changes as prescribed in Section I of Appendix II and minor changes as prescribed in Section II.1 of Appendix II issued together with this Circular, within one month from the date of receipt of complete files, the file receiving agency shall issue a document agreeing or disagreeing with the changes and supplements to the drug circulation registration certificate, specifically as follows:

"a) Within five days from the date of receiving all necessary documents, the agency receiving the documents shall transfer the documents to the experts for review;"

b) Within fifteen days from the date the expert gives an opinion, the Minister of Health authorizes the Director of the Traditional Medicine Management Department to issue a document agreeing or disagreeing with the changes and supplements to the drug circulation registration certificate for files that meet the requirements.

5. In cases where the file does not meet the requirements stipulated in Article 28 of this Circular, during the file examination period for changes and supplements, the receiving agency must promptly provide specific guidance for the registering entity to modify and supplement the file until it meets the requirements. The time and number of times the registering entity modifies and supplements the file according to Clause 9 of Article 4 of this Circular.”

29. Supplement Clause 7 Article 31 is as follows:

"7. The time limit for implementing changes and supplements to the drug material circulation registration certificate shall not exceed six months from the date the Director of the Traditional Medicine Management Department issues the approval letter, except where the Traditional Medicine Management Department has other requirements."

30. Add Clause 8 Article 31 is as follows:

"8. In some cases of change and supplement, the registrant and the manufacturer of drug materials may update the label themselves without submitting an application or notifying the Traditional Medicine Management Department, including the following cases:

a) Implementing the labeling of drug materials as prescribed in Clause 2, Article 35 of Circular No. 01/2018/TT-BYT dated January 18, 2018, issued by the Ministry of Health on drug labeling and instructions for use;

b) Implementing changes and supplements to the drug material label according to the content specified in the request document of the Traditional Medicine Management Department;

"c) Other contents:"

- Changing the information of the drug material importer on the label;

- Correcting typographical errors on the label;

- Supplementing quality standard information on the label based on the approved dossier by the Traditional Medicine Management Department;

- Other changes and supplements according to the notification results of the dossier review issued by the Traditional Medicine Management Department."

31. Add Point c Clause 1, Article 32 as follows:

"c) Drug materials used to produce medicines to meet urgent needs for national defense, security, epidemic prevention, disaster relief, and special treatment needs."

32. Amend and supplement Clause 2, Article 32 as follows:

"2. Documents and procedures for drug materials under priority shortened processing time:

a) Within four months from the date of receipt of all documents, the receiving agency shall implement the procedures as stipulated in Clauses 3, 4, and 5 of Article 29 of this Circular for drug materials prioritized for shortened processing time as provided in Points a and b of Clause 1 of this Article.

b) Within one month from the date of receipt of all documents, the receiving agency shall implement the procedures as stipulated in Clauses 3, 4, and 5 of Article 29 of this Circular for drug materials prioritized for shortened processing time as provided in Point c of Clause 1 of this Article."

33. Amend Clause 1, Article 36 as follows:

"1. The Minister of Health shall establish an Advisory Council for issuing circulation registration certificates for traditional medicine and drug materials. The Advisory Council shall consist of: the Chairman; Vice Chairmen; Members; and the Standing Office as the Secretariat."

34. Amend Clause 4, Article 37 as follows:

"4. The Traditional Medicine Management Department shall develop and promulgate regulations on criteria for selecting, organizing, and operating expert groups for dossier review; sign contracts with reviewing experts or units participating in the organization of reviews; organize training courses for reviewing experts; conduct evaluations of professional competence and compliance with regulations to adjust and supplement reviewing experts appropriately."

35. Add Clause 5 Article 37 as follows:

"5. The costs of organizing dossier reviews shall be implemented in accordance with the provisions of the law."

36. Amend and supplement Appendix II attached to this Circular.

Article 2. Effective Date

This Circular takes effect from February 15, 2022.

Article 3. Transitional Provisions

Applications submitted before the effective date of this Circular shall continue to be processed in accordance with Circular No. 21/2018/TT-BYT dated September 12, 2018, issued by the Minister of Health on the registration of circulation of traditional medicine and drug materials.

Article 4. Reference Provisions

In case the regulatory legal documents and provisions cited in this Circular are amended, supplemented, or replaced, they shall be implemented according to the new regulatory legal documents.

Article 5. Responsibilities for Implementation

The Head of the Ministry's Office, the Inspector General, Heads of Departments, Directors of the Traditional Medicine Management Department, Directors of subordinate units of the Ministry of Health, Provincial and Municipal Health Departments, drug business establishments, and other relevant agencies, organizations, and individuals are responsible for implementing this Circular.

During implementation, if there are difficulties or obstacles, agencies, organizations, and individuals should promptly report them to the Traditional Medicine Management Department, Ministry of Health for consideration and resolution./.