Chương III Thông tư 08/2022/TT-BYT: Hồ sơ đăng ký thuốc, nguyên liệu làm thuốc

Chapter III

MARKETING APPLICATION

Section 1. APPLICATION FOR ISSUANCE, RENEWAL, REVISION OF MARKETING AUTHORIZATION OF DRUGS/MEDICINAL MATERIALS

Article 22. Documents in application for issuance, renewal, revision of marketing authorization of drugs/medicinal materials

1. Documents issued by foreign competent authorities shall bear consular legalization in accordance with regulations of law on consular legalization, except for the cases in which consular legalization is exempted by law.

2. Licenses, certificates, confirmations, registration certificates (hereinafter referred to as “legal documents”) that have effective dates written thereon must be effective on the date of receipt of the application (according to the receipt note). In case the CPP does not specify the effective period, it will be 24 months from the issuance date.

3. Legal documents:

a) Original copies shall bear signatures and names of the signers and seals of competent authorities of the certifying country; certified true copies shall be authenticated by Vietnamese competent authorities or organizations in accordance with Vietnam’s regulations of law on document authentication. Original copies shall be presented for verification purposes where necessary;

b) In case a legal document is an electronic document, which does not have to bear the signature and name of the signer or seal of the competent authority of the certifying country, the applicant shall submit one of the following documents:

- The original copy or certified true copy of the legal document which has been certified by the foreign competent authority and bears consular legalization as per regulations;

- The legal document search result from a website or English database of the issuing authority or competent authority of the foreign country which bear the applicant's seal enclosed with the document providing information about the search link. This shall be sent to the Drug Administration of Vietnam. The applicant shall bear legal responsibility for the legitimacy and accuracy of these documents, information and search result.

4. CPP:

a) The CPP must be issued by a competent authority and contains sufficient information according to the model certificate published on WHO's website (https://www.who.int).

b) The CPP shall bear the signature and name of the signer, and seal of the issuing authority. In case the CPP does not bear the seal of the competent authority of the certifying country, the applicant shall provide documents proving that the CPP does not have to bear the seal according to the certifying country's regulations.

c) For generic drugs, herbal drugs and probiotics, and drugs whose marketing authorization is renewed or revised:

There has to be 01 CPP issued by the competent authority of the manufacturing country certifying that the drug is granted marketing authorization and marketed in reality in such country.

If the drug has not yet been granted the marketing authorization in the country of origin or has been granted the marketing authorization but has not been marketed in reality in the country of origin, the applicant shall provide 01 legal document which is issued by the regulatory authorities prescribed in Clause 9 Article 2 of this Circular which certifies that the drug has been granted the marketing authorization and marketed in reality in such country and contains the following mandatory information: name of drug, active ingredients, concentration or content of active ingredients, dosage form, name and address of the manufacturer.

d) Regarding new modern medicines, vaccines, biologicals that are imported, except probiotics:

There has to be 01 CPP issued by the competent authority of the manufacturing country certifying that the drug is granted marketing authorization and marketed in reality in such country.

In case the issuing authority is one of the regulatory authorities specified in Clause 9 Article 2 of this Circular, only 01 CPP has to be submitted.

In case the issuing authority is not one of the regulatory authorities specified in Clause 9 Article 2 of this Circular, the applicant shall provide legal documents issued by the regulatory authorities prescribed in Clause 9 Article 2 of this Circular certifying that the drug has been granted the marketing authorization and marketed in reality in such country and contains the following mandatory information: name of drug, active ingredients, concentration or content of active ingredients, dosage form, name and address of the manufacturer, or documents proving that the drug in on WHO's prequalified list of medicines.

dd) Regarding drugs applied for classification of proprietary drugs or reference biologicals

There has to be 01 CPP issued by the competent authority of the manufacturing country certifying that the drug is granted marketing authorization and marketed in reality in such country.

In case the issuing authority is one of the regulatory authorities specified in Clause 9 Article 2 of this Circular, only 01 CPP has to be submitted.

In case the issuing authority is not one of the regulatory authorities specified in Clause 9 Article 2 of this Circular, the applicant shall provide legal documents issued by the regulatory authorities prescribed in Clause 9 Article 2 of this Circular certifying that the drug has been granted the marketing authorization and marketed in reality in such country and contains the following mandatory information: name of drug, active ingredients, concentration or content of active ingredients, dosage form, name and address of the manufacturer.

e) In case an imported drug, vaccine or biological does not have a CPP that satisfies the requirements specified in Point c and Point d of this Clause, the Minister of Health of Vietnam, on the basis of opinions provided by the Advisory Board, shall make the decision if the drug/vaccine/biological has been granted the marketing authorization by at least one regulatory authority in any country and satisfies any of the following requirements:

- The drug/vaccine/biological is meant to serve national defense and security, epidemic control, disaster recovery or a state-level health program;

- The vaccine is meant for the national expanded immunization program and another substitute vaccine with equivalent quantity, safety, efficacy or cost is not available on the domestic market;

- In other cases under a mutual recognition agreement between competent authorities in terms of conditions for manufacturing and marketing of drugs, vaccines and biologicals.

g) The information displayed on the CPP must be consistent with relevant information in the marketing application. In case information on the CPP is not consistent with that in the marketing application, the applicant shall provide documentary explanation and evidence.

5. The application form and other administrative documents must bear signatures and seals. Signature seals are not permitted. Applicants and manufacturers may use digital signatures on their documents. The registration and use of digital signatures shall comply with the Government’s Decree No. 130/2018/ND-CP dated September 27, 2018. These documents shall be signed by one of the following persons:

a) The President of the Member Board or Board of Directors; the General Director, chief executive officer, or director of the applying or manufacturing establishment;

b) An assigned person according to the company's charter, authorization letter or other documents proving the authority of the signer;

c) Persons authorized to sign these documents by the persons specified in Point a or Point b of this Clause.

6. Regulations on authorization letter:

a) The document authorizing a person to act as the applicant shall have the following information:

- Name and address of the product license holder/marketing authorization holder or the authorizing manufacturer;

- Name and address of the authorized applicant;

- Name of the drug, concentration or content of active ingredients; dosage form;

- Authorization content.

In case the authorization involves multiple drugs, the authorization letter shall have a list of drugs with adequate information as mentioned above.

The authorization letter of a foreign applicant must bear consular legalization as per regulations. The authorization letter must be the original copy or an authenticated copy.

a) The document authorizing a person to sign the marketing application shall have the following information:

- Name and address of the applying establishment;

- Names and positions of the authorizing person and authorized person;

- Name of the drug, concentration or content of active ingredients; dosage form;

- Authorization content.

- Effect of the authorization letter.

In case the authorization involves multiple drugs, the authorization letter shall have a list of drugs with adequate information as mentioned above.

In case the person authorized to sign the application is not the representative office manager, the authorization letter shall bear the seal and signature of the manager of the representative office in Vietnam.

The authorization letter shall be the original copy or a copy bearing the seal of the representative office (for foreign applicants) or the Vietnamese applicant.

c) Quantity of authorization letters in an application:

- In case the applicant is not the manufacturer, each application shall include one authorization letter bearing the name of the applicant;

- In case the position of the person who signs the application is not one of those specified in Point a and Point b Clause 5 of this Article, each application shall include one document authorizing that person to sign the application.

7. The Certificate of Eligibility for Pharmacy Business which permits manufacture, wholesaling, export or import of drug/medicinal material (for Vietnamese applicants).

8. The license to establish a representative office in Vietnam.

If the name or address of the applicant on the license to establish a representative office in Vietnam is different from those on the legal documents issued by foreign authorities, documentary evidence must be provided.

9. For foreign applicants: Legal documents issued by foreign authorities permitting at least one of the following: manufacture, wholesaling, export, import of drugs/medicinal materials.

In cases where the applicant is also the manufacturer written on the CPP, the legal documents mentioned in this Clause are not required.

In cases where the license for manufacture, wholesaling, export or import of drugs/medicinal materials is not issued in any country, it is required to have the business license for business registration certificate that permits manufacture, wholesaling, export or import of drugs/medicinal materials and a certification issued by a competent authority that the applicant is qualified and is operating in the pharmaceutical field, or a certificate of Good Manufacturing Practice, Good Distribution Practice, Good Supply Practice or Good Storage Practice.

In case of medicinal materials: if the home country does not grant licenses to traders of medicinal materials, other licenses available in the home country may be accepted if they permit manufacture, wholesaling, export or import of medicinal materials.

10. If the applicant is already included in the list of applicants for drugs/medicinal materials posted on the website of the Drug Administration of Vietnam, the documents mentioned in Clause 7, 8, 9 of this Article are not required.

11. Documents proving compliance with GMP guidelines submitted by a manufacturer of active ingredients, excipients, capsule shells, semi-finished herbal ingredients and herbal ingredients (for manufacture of herbal drugs) may be any of the following documents:

a) The GMP certificate;

b) The manufacture license that certifies GMP compliance;

c) The CPP if the active ingredient is conformable with GMP;

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

dd) For excipients in marketing applications of drug products or semi-finished medicinal materials:

In case the documents specified in Point a, b or d of this Clause cannot be provided, the manufacturer of drug products or semi-finished drug shall carry out self-evaluation of GMP for excipients manufacturers according to regulations in 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, which is amended by Points a, b, and dd Clause 6 Article 1 of Circular No. 29/2020/TT-BYT, include in the marketing application a self-declaration of GMP conformity, and take legal responsibility for such declaration according to Form No. 10/TT enclosed herewith;

e) For herbal ingredients in marketing applications:

In case the documents specified in Point a and Point b of this Clause cannot be provided, the applicant shall provide a certification of Good Agricultural and Collection Practice (GACP);

g) Other legal documents provided by competent authorities shall have the following mandatory information: name and address of the manufacturer, certification of GMP compliance and names of the active ingredients/excipients/capsule shells/semi-finished and finished herbal ingredients.

12. The label sample and package insert of the drug marketed in reality in the country of manufacture or the country in which the CPP is issued (certifying country) bearing the seal of the representative office, the applicant or the manufacturer (color prints are accepted if the colors thereon match those on the labels marketed in the home country. If the package insert of the drug marketed in the country of origin is not written in English, a Vietnamese translation bearing the seal of the representative office, applicant or manufacturer is required.

13. The label sample, the package insert of the drug to be marketed in Vietnam shall comply with regulations of the Minister of Health of Vietnam on labeling of drugs/medicinal materials and the following requirements:

a) The label sample and package insert shall bear the seal of the representative office, applicant or manufacturer;

b) The secondary package shall have a bar code, QR code or DataMatrix Code (DMC) in accordance with Point l Clause 1 Article 48 of this Circular.

14. If the manufacturer is already included in the list of GMP manufacturers posted on the website of the Drug Administration of Vietnam, the GMP documents are not required.

15. Specifications, test method, test report and stability study documents (for both active ingredients and drug product) shall be original copies bearing the seal of the manufacturer; in case there are multiple establishments participating in the manufacture of the product, the seal of the establish responsible for quality inspection of the drug or batch shall be accepted; copies shall bear the seal of the applicant (or representative office of the foreign applicant).

In case the application of an active ingredient does not bear the seal of its manufacture, the drug product manufacturer shall append its seal and take legal responsibility for the accuracy, legitimacy and truthfulness of this document.

The test report shall contain: name and address of the manufacturer, certificate number, name and signature of the responsible person, issuance date of the certificate), information about the drug/medicinal material (name, batch number, expiry date, applied standards, specifications, analysis result, conclusion on quality of the batch).

16. The test report, results of validation of specifications and test method in Vietnam:

For manufacturers that have not applied GMP under the roadmap of the Ministry of Health of Vietnam or those required by the Drug Administration of Vietnam according to Appendix III hereof, the test report, results of validation of specifications and test method in Vietnam shall be certified by a state-owned drug testing laboratory that satisfies GLP requirements or a profitable drug testing laboratory that has a certificate of eligibility (original copy or certified true copy).

17. The certificate that the medicinal material is permitted to be manufactured or marketed in the country of origin, on which the following information is mandatory: name of the ingredient, name and address of the manufacturer, the country of origin, signature and full name of the signer.

Article 23. Administrative documents in application for issuance, renewal, revision of marketing authorization of drugs/medicinal materials

1. Administrative documents in an application for marketing authorization of a new modern drug, vaccine or biological consists of:

a) Form No. 5/TT enclosed herewith;

b) The document authorizing a person to act as applicant (if any);

c) The document authorizing a person to sign the application (if any);

d) The label sample, the package insert of the to-be-marketed drug.

dd) The Certificate of Eligibility for Pharmacy Business (for Vietnamese applicants);

e) Legal documents, the license to establish a representative office in Vietnam (for foreign applicants);

g) Summary of product properties for new modern drugs, vaccines and biologicals (Form No. 6/TT enclosed herewith);

h) Legal documents of the manufacturer of active ingredients, excipients, capsule shells, semi-finished and finished herbal ingredients;

i) The certificate of the testing laboratory in the cases specified in Clause 16 Article 22 of this Circular;

k) The risk management plan (for vaccines) according to Form No. 7/TT enclosed herewith;

l) The label sample and the package insert of the drug being marketed in reality in the country of origin or the country in which the CPP is issued (for foreign applicants);

m) The CPP (for foreign applicants);

n) Assessment of GMP compliance in the cases mentioned in Article 95 of Decree No. 54/2017/ND-CP for foreign drug/medicinal material manufacturers applying for the marketing authorization in Vietnam (unless the applicant GMP compliance has been published on the website of Drug administration of Vietnam or the application has submitted an application for GMP assessment by Drug Administration of Vietnam).

2. Administrative documents of the application for marketing authorization of generic drugs, herbal drugs, medicinal materials shall comply with regulations of Points a, b, c, d, dd, e, h, i, l, m, n Clause 1 of this Article (an application for marketing authorization of a medicinal material manufactured in a foreign country also requires the certificate that the medicinal material is approved for manufacture or marketing in such country).

3. Administrative documents of the application for renewal of marketing authorization modern drugs, vaccines, biologicals, herbal drugs, medicinal materials include those specified in Points a, c, dd, e, m, n Clause 1 of this Article and the following documents:

a) The document authorizing a person to act as applicant in case of change of applicant when the application is submitted;

b) The marketing report according to Form No. 8/TT enclosed herewith;

c) A copy of the marketing authorization granted in Vietnam;

d) The report on monitoring and evaluation of safety and efficacy of the drug according to Form No. 2/TT enclosed herewith if the renewal requires such a report according to Clause 2 Article 5 of this Circular;

dd) The certificate that the medicinal material is permitted to be manufactured or marketed in the country of origin (for medicinal materials that are manufactured in foreign countries).

4. Administrative documents of the application for revisions to marketing authorization modern drugs, vaccines, biologicals, herbal drugs, medicinal materials are those specified in Point a and Point c Clause 1 of this Article.

5. Administrative documents of the application for marketing authorization following simplified validation procedures are those specified in Points a, b, c, d, dd, e, h, i, l, m Clause 1 of this Article.

Section 2. APPLICATION FOR ISSUANCE, RENEWAL, REVISION OF MARKETING AUTHORIZATION OF MODERN DRUGS, VACCINES AND BIOLOGICALS

Article 24. Quality documents in application for issuance or revision of marketing authorization of modern drugs, vaccines and biologicals

Quality documents shall comply with Part II – ACTD or 3-ICH-CTD and the following regulations:

1. For vaccines, antiserum, blood extracts and human plasma:

a) The batch release certificate issued by a competent authority of the country in which the CPP is issued or one of the regulatory authorities specified in Clause 9 Article 2 of this Circular;

b) The test report, specifications and test method certified by National Institute for Control of Vaccines and Biologicals (NICVB).

2. For rare drugs, drugs serving national defense and security, epidemic control, disaster recovery, and drugs serving special treatment:

a) Rare drugs for treatment of rare diseases: existing stability studies according to ASEAN or ICH guidelines;

b) Drugs serving national defense and security, epidemic control or disaster recovery:

Stability study data existing at the submission date shall be accepted for consideration of expiry date of the drug according to opinions given by the Advisory Board if the time period of stability study data fails to meet the minimum study period requirement laid down in ASEAN guidelines.

After obtaining the marketing authorization, the applicant shall continue submit stability study documents of finished product, until the minimum period of stability study is satisfied according to ASEAN guidelines, to the Drug Administration of Vietnam in the form of modification as prescribed in Appendix II enclosed herewith for considering and updating the expiry date as prescribed.

If the stability study result of the drug fails to meet the study proposal included in the marketing application, the applicant shall submit a report to the Drug Administration of Vietnam for submission to the Advisory Board for considering the drug’s expiry date.

Based on opinions given by the Advisory Board, the Drug Administration of Vietnam shall decide the expiry date of drug, including the batch of drugs manufactured, according to actual stability study data.

c) Drugs serving special treatment: existing stability study data according to ASEAN or ICH guidelines which is decided by the Minister of Health of Vietnam on the basis of opinions provided by the Advisory Board if the applicant proves that the drug cannot be stored in climatic zone IVb according to ASEAN guidelines.

3. If the manufacturer uses medicinal materials that are have been granted marketing authorization in Vietnam:

a) Quality documents of the materials and the documents mentioned in Point h Clause 1 Article 23 of this Circular are not required in the application for marketing authorization of the drug product;

b) The applicant shall submit the following documents:

- 01 test report of the medicinal materials provided by the drug product manufacturer the specifications in which are equivalent to or higher than those of the medicinal material manufacturer. Where the drug product manufacturer is unable to inspect all specifications, it shall provide test reports of remaining indicators provided by state testing bodies or testing laboratories granted certificate of eligibility for pharmacy business;

- 01 test report of the medicinal materials provided by the medicinal material manufacturer.

4. For simplified validation procedures:

a) Documents about active ingredients:

- Names of the active ingredients (international nonproprietary names);

- Name and address of the manufacturer of the active ingredients and semi-finished product that contain the active ingredients;

- Specifications and method for testing of the active ingredients and semi-finished product that contain the active ingredients. If a Vietnam’s pharmacopoeia or a reference pharmacopoeia accepted by the Ministry of Health of Vietnam is applied, only the name of the pharmacopoeia is required;

- 01 test report of active ingredients and semi-finished products provided by the manufacturer thereof, and 01 test report of active ingredients and semi-finished products provided by the manufacturer of the drug product;

- For semi-finished active ingredients, the manufacturer shall provide their formula and manufacturing process.

b) Documents about the drug product:

- The description and composition shall comply with Part 1 of ACTD;

- Specifications and method for testing of the drug product. If Vietnam’s pharmacopoeia or a reference pharmacopoeia accepted by the Ministry of Health of Vietnam is applied, only the name of the pharmacopoeia is required;

- Manufacture of the drug product: batch formula, manufacturing process and process controls; control of critical steps and intermediates.

- Test report of drug product;

- Primary package: appearance, materials and specifications;

- Stability study report of the drug product.

c) Other quality documents shall comply with Part II of ACTD or 3-ICH-CTD and shall be retained by the applicant and manufacturer.

5. The documents mentioned in this Article shall:

a) comply with regulations of Appendix I hereof, including:

- ACTD;

- Guideline for stability study;

- Guideline for manufacturing process validation;

- Guideline for analytical method validation;

- Guideline on bioavailability and bioequivalence study;

b) Documents that are prepared according to ICH-CTD and guidelines thereof are not required to be converted to the requirements in Point a of this Clause;

c) If the Certificate of Suitability to the monographs of the European Pharmacopoeia (CEP) is available: the active ingredient documents specified in Points a, b of this Clause may be replaced by the following documents:

- CEP accompanied by all appendixes issued by the European Directorate for the Quality of Medicines & HealthCare (EDQM);

- Analytical data of the batch of active ingredients;

- If the time limit for re-inspecting quality of the active ingredients is not specified in CEP, the stability study data of the active ingredients shall be submitted.

Article 25. Pre-clinical documents in application for issuance, renewal or revision of marketing authorization of modern drugs, vaccines or biologicals

Pre-clinical documents shall comply with Part III or ACTD or 4-ICH-CTD.

Pre-clinical documents are not required for probiotics with origins, bacterial strain, concentration or content, indications, doses that are similar to biologicals licensed by one of the regulatory authorities specified in Clause 9 Article 2 of this Circular.

Article 26. Clinical documents in application for issuance, renewal or revision of marketing authorization of modern drugs, vaccines or biologicals

Clinical documents shall comply with Part IV or ACTD or 5-ICH-CTD.

Clinical documents are not required for probiotics with origins, bacterial strain, concentration or content, indications, doses that are similar to biologicals licensed by one of the regulatory authorities specified in Clause 9 Article 2 of this Circular.

Article 27. Application for issuance, renewal or revision of marketing authorization of modern drugs, vaccines or biologicals

1. An application for issuance of marketing authorization of a new modern drug, vaccine or biological consists of:

a) The administrative documents specified in Clause 1 Article 23 of this Circular.

b) The quality documents specified in Article 24 of this Circular;

c) The pre-clinical documents specified in Article 25 of this Circular;

d) The clinical documents specified in Article 26 of this Circular;

dd) For proprietary drugs or reference biologicals: the documents specified in Points a, b, c, d Clause 1 of this Article and Paragraph 2 Point a Clause 1 Article 9 of this Circular.

2. An application for issuance of marketing authorization of a generic drug consists of:

a) The administrative documents specified in Clause 2 Article 23 of this Circular;

b) The quality documents specified in Article 24 of this Circular.

3. An application for renewal of the marketing authorization consists of:

a) The administrative documents specified in Clause 3 Article 23 of this Circular;

b) Relevant documents specified in Appendix II enclosed herewith in case there are changes in the administrative documents of the drug (excluding changes in samples of the label and package insert).

If the applicant has submitted the new administrative documents before the renewal application, they are not required in the renewal application even if they are yet to be approved.

4. An application for revision of the marketing authorization consists of:

a) The administrative documents specified in Clause 4 Article 23 of this Circular;

b) Documents suitable for the major variations and minor variations specified in Appendix II enclosed herewith. For vaccines of the same manufacturer or product license holder or marketing authorization holder, the manufacturing location may be changed within or outside the country in which the marketing authorization is granted.

5. An application for marketing authorization following simplified procedures consists of:

a) The administrative documents specified in Clause 5 Article 23 of this Circular;

b) The quality documents specified in Point a and Point b Clause 4 Article 24 of this Circular.

Section 3. APPLICATION FOR ISSUANCE, RENEWAL, REVISION OF MARKETING AUTHORIZATION OF HERBAL DRUGS

Article 28. Quality documents in application for issuance, renewal or revision of marketing authorization of herbal drugs

1. Ingredients

a) The manufacturing process (only applied to herbal ingredients): detailed and adequate description of the preparation and processing of herbal ingredients. For semi-finished herbal ingredients and bone glue, it is required to describe in details the manufacturing process thereof, except for those that have been granted marketing authorization;

b) Specifications and test method

- For herbal ingredients other than semi-finished herbal ingredients: follow instructions in Circular No. 38/2021/TT-BYT;

- Regulations on specifications and test methods for herbal ingredients other than semi-finished herbal ingredients specified in Circular No. 38/2021/TT-BYT shall also be applied to semi-finished herbal ingredients.

c) Test report of ingredients

- 01 test report of herbal ingredients provided by the manufacturer of the drug product. Where the drug product manufacturer is unable to inspect all specifications, it shall provide test reports of remaining indicators provided by state testing bodies or testing laboratories granted certificate of eligibility for pharmacy business;

- 01 test report of semi-finished herbal ingredients and bone glue provided by the manufacturer thereof, and 01 test report of semi-finished herbal ingredients and bone glue provided by the manufacturer of the drug product.

2. Drug product

a) Manufacturing process

- Formula of a smallest packaging unit: name, content, concentration, weight, specifications of each ingredient in a smallest packaging unit. If the drug product is made of semi-finished herbal ingredients or bone glue, it is required to specify the ratio of herbal ingredients to total weight of semi-finished herbal ingredients or bone glue, the the ratio of bone glue or semi-finished herbal ingredients to the initial herbal ingredients and content (%) of the active ingredients or substances therein;

- Batch formula: names, weights, volumes of each ingredient in the formula;

- Manufacturing process diagram: present all stages in the manufacturing process, including the path of ingredients and its consistency with the manufacturing process description;

- Manufacturing process description: describes in details every step of the manufacturing process, including specifications thereof;

- Equipment list: names, specifications and uses of each equipment;

- Control of manufacturing process: Describe in details control criteria for each stage, including the criterion, specifications, control method, control frequency and sample size;

b) Specifications and test method

- Formula of a smallest packaging unit: name, content, concentration, weight, specifications of each ingredient in a smallest packaging unit. If the drug product is made of semi-finished herbal ingredients or bone glue, it is required to specify the ratio of herbal ingredients to total weight of semi-finished herbal ingredients or bone glue, the the ratio of bone glue or semi-finished herbal ingredients to the initial herbal ingredients and content (%) of the active ingredients or substances therein;

- Specifications of drug product: comply with the Circular No. 11/2018/TT-BYT;

c) The test report of drug product;

d) Specifications of packages: Describe in details the material, specifications, quality and test method;

dd) A stability study report according to the guidelines for stability study in Appendix I enclosed herewith.

Article 29. Safety and efficacy documents in application for issuance, renewal or revision of marketing authorization of herbal drugs

1. Safety and efficacy documents of herbal drugs shall comply with regulations in Appendix V enclosed herewith, ACTD or ICH-CTD.

2. The documents specified in Point b Clause 1 Article 18 of this Circular (if any).

Article 30. Application for issuance, renewal, revision of marketing authorization of herbal drugs

1. An application for issuance of marketing authorization of a herbal drug consists of:

a) The administrative documents specified in Clause 2 Article 23 of this Circular;

b) The quality documents specified in Article 28 of this Circular;

c) The safety and efficacy documents specified in Article 29 of this Circular;

2. An application for renewal of marketing authorization of a herbal drugs consists of:

a) The administrative documents specified in Clause 3 Article 23 of this Circular;

b) Relevant documents specified in Section D Appendix II enclosed herewith in case there are changes in the administrative documents of the drug at the time of application for renewal of the marketing authorization (excluding changes in samples of the label and package insert).

If the applicant has submitted the new administrative documents before the renewal application, they are not required in the renewal application even if they are yet to be approved.

3. An application for revision of the marketing authorization of a generic drug consists of:

a) The administrative documents specified in Clause 4 Article 23 of this Circular;

b) Documents about major variations and minor variations according to Section D Appendix II enclosed herewith.

Section 4. APPLICATION FOR MARKETING APPLICATION OF MEDICINAL MATERIALS

Article 31. Quality documents in application for issuance, renewal or revision of marketing authorization of medicinal materials

1. For active ingredients: Documents of active ingredients specified in ACTD. Submit the Drug Master File if the manufacturer’s specifications are applied.

2. For semi-finished active ingredients: The same documents specified in ACTD as those of drug products, in which the documents about the drug product will be replaced with documents about the semi-finished products; the formula of a single dose or smallest packaging unit will be replaced with the batch formula.

3. For semi-finished herbal ingredients, excipients and capsule shells:

a) Formula of the semi-finished herbal ingredients, pre-mixed excipients, capsule shells: composition, weight, volume, specifications of each component of the formula. For ingredients derived from animals, information should be provided regarding adventitious agents (viral safety data);

b) Manufacturing process

- Manufacturing process diagram: describes all stages in the manufacturing process, including the path of ingredients and its consistency with the manufacturing process description;

- Manufacturing process description: describes in details every step of the manufacturing process, including specifications thereof;

- Equipment list: names, specifications and uses of each equipment;

- Control of manufacturing process: Describe in details control criteria for each stage, including the criterion, specifications, control method, control frequency and sample size.

c) Specifications and test method

- Regulations on specifications and test methods for herbal ingredients other than semi-finished herbal ingredients specified in Circular No. 38/2021/TT-BYT shall also be applied to semi-finished herbal ingredients;

- Specifications of excipients and capsule shells shall comply with Circular No. 11/2018/TT-BYT.

d) The test report;

dd) Specifications of packages: Describe in details the material, specifications, quality and test method;

e) The stability study report, including the stability study proposal, data, result and discussion.

Article 32. Application for issuance, renewal, revision of marketing authorization of medicinal materials

1. An application for issuance of marketing authorization of a medicinal material consists of:

a) The administrative documents specified in Clause 2 Article 23 of this Circular;

b) The quality documents specified in Article 31 of this Circular.

2. An application for renewal of marketing authorization of a medicinal material consists of:

a) The administrative documents specified in Clause 3 Article 23 of this Circular;

b) Relevant documents according to Section B of Appendix II enclosed herewith if there are changes to the administrative documents of the medicinal material at the time of application for renewal of the marketing authorization (excluding changes in samples of the label).

If the applicant has submitted the new administrative documents before the renewal application, they are not required in the renewal application even if they are yet to be approved.

3. An application for revision of the marketing authorization of a medicinal material consists of:

a) The administrative documents specified in Clause 4 Article 23 of this Circular;

b) Documents about major variations and minor variations according to Section B Appendix II enclosed herewith.