Circular No. 11/2021/TT-BYT guiding the registration for circulation of COVID-19 vaccines in emergency situations.

CIRCULAR

GUIDELINES FOR REGISTRATION AND CIRCULATION OF COVID-19 VACCINES IN EMERGENCY SITUATIONS

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

Pursuant to the Technology Transfer Law No. 07/2017/QH14 dated June 19, 2017;

Pursuant to the Law on Legislative Regulatory Acts No. 80/2015/QH13 dated June 22, 2015, and the Law Amending and Supplementing Certain Provisions of the Law on Legislative Regulatory Acts No. 63/2020/QH14 dated June 18, 2020;

Pursuant to Resolution No. 30/2021/NQ-QH15 dated July 28, 2021 of the National Assembly, Fifteenth Session;

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

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;

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 Resolution No. 86/NQ-CP dated August 6, 2021 of the Government on urgent measures to prevent and control the COVID-19 pandemic to implement Resolution No. 30/2021/QH15 dated July 28, 2021 of the National Assembly, Fifteenth Session;

At the proposal of the Director of the Drug Administration Department;

The Minister of Health issues this Circular guiding the registration for circulation of COVID-19 vaccines in emergency situations.

PART I

GENERAL PROVISIONS

Article 1. Scope of Regulation

This Circular stipulates in detail the procedures for registering the circulation of COVID-19 vaccines (hereinafter referred to as vaccines) in emergency situations:

1. Documents, procedures for issuing, extending, changing, and supplementing the vaccine circulation registration certificate.

2. Requirements for clinical data in the registration dossier to ensure the safety and efficacy of the vaccine.

3. In cases where one or several phases of clinical trials of the vaccine are exempted, the vaccine must undergo Phase 4 clinical trials in Vietnam.

Article 2. Interpretation of Terms

In this Circular, the following terms are understood as follows:

1. The technology transfer entity for vaccine production is the entity that owns the technology or has the right to use the vaccine production technology according to the law and transfers ownership rights or technology usage rights to the recipient entity for application in one, some, or all stages of the production process.

2. The recipient entity for vaccine production technology transfer is the entity that receives ownership rights or the right to use the vaccine production technology from the technology transfer entity according to the agreement between both parties for application in one, some, or all stages of the production process.

3. Transferred technology vaccine is the vaccine produced by the recipient entity for vaccine production technology transfer, in which one, some, or all stages of the vaccine production process apply transferred production technology according to the agreement between both parties.

4. Pre-transfer technology vaccine is the vaccine that already has a circulation registration certificate in Vietnam or does not have a circulation registration certificate in Vietnam, ensuring quality, safety, and efficacy, and is transferred by the technology transfer entity for vaccine production to the recipient entity for vaccine production technology transfer for application in one, some, or all stages of the production process.

Article 3. Rights and responsibilities of the entities registering, producing, transferring, and receiving vaccine production technology

1. The entity registering the vaccine shall perform its rights and responsibilities as prescribed in Article 57 of the Medicine Law No. 105/2016/QH13 dated April 6, 2016 (hereinafter referred to as the Medicine Law) and Article 3 of Circular No. 32/2018/TT-BYT dated November 12, 2018 of the Ministry of Health on the registration for circulation of medicines and raw materials for medicines (hereinafter referred to as Circular No. 32/2018/TT-BYT).

2. The entity producing the vaccine shall perform its rights and responsibilities as prescribed in Article 43 of the Medicine Law and Article 4 of Circular No. 32/2018/TT-BYT.

3. The entity transferring vaccine production technology and the entity receiving vaccine production technology transfer shall perform their rights and responsibilities as prescribed in the Technology Transfer Law No. 07/2017/QH14 dated June 19, 2017 and related regulatory acts.

4. The registering entity shall be responsible for coordinating with the producing entity:

a) To comply with Clause 2, Clause 3, Article 11 and Clause 1, Article 13 of this Circular for vaccines lacking complete clinical data;

b) To establish a comprehensive pharmacovigilance system for the product in accordance with regulations and report adverse reactions following vaccination fully to the Preventive Medicine Department;

c) To ensure compliance with risk management plans throughout the entire lifecycle of the vaccine.

Article 4. Provisions on monitoring, evaluation reports on safety and efficacy

1. Drug business establishments, medical examination and treatment facilities, vaccination centers, provincial disease control centers under the central government must implement monitoring, supervision, data collection, consolidation, assessment, and report to competent state management agencies on adverse events following immunization and other related information as prescribed in Articles 77 and 78 of the Medicine Law, National Guidelines on Pharmacovigilance, and relevant regulations.

2. Vaccine registration entities must submit safety and efficacy evaluation reports for vaccines according to Appendix 01 of this Circular:

a) Submit periodic safety and efficacy evaluation reports every two months during the validity period of the vaccine registration certificate to the National Center for Medicines Information and Adverse Reaction Monitoring (hereinafter referred to as the National DI & ADR Center) and the Preventive Health Department.

b) When submitting an application for extending the validity of the registration certificate at the Drug Administration Department.

Article 5. Language, form, number of applications, and documents

1. The language, form, number of applications, and documents for vaccine registration shall be implemented in accordance with the provisions of Clause 1, Clause 2, Clause 4, and Clause 5 of Article 6 of Circular No. 32/2018/TT-BYT.

2. Vaccines may be registered in the same application if they share the following common factors: vaccine name, dosage form, route of administration, vaccine quality standards, the same formulation, including the same drug substance concentration or content.

3. Provisions on the application of online forms:

a) Number and components of the application: one complete electronic application in accordance with this Circular for online registration and one administrative paper copy of the application (excluding labels and user instructions for vaccines) to the Drug Administration Department.

b) Registration entities and manufacturers can use digital signatures to sign related documents of the registration entity and manufacturer. The registration and use of digital signatures shall be carried out in accordance with the provisions of Government Decree No. 130/2018/NĐ-CP dated September 27, 2018, detailing the implementation of the Law on Electronic Transactions regarding digital signatures and digital signature certification services.

c) The timeline for applying online forms will be announced by the Minister of Health.

Article 6. Fees for vaccine registration

Vaccine registration entities must pay fees related to vaccine registration in accordance with current laws on fees and charges.

Article 7. Effectiveness, symbols of the vaccine registration certificate, time limit for submitting extension registration applications, label and user guide models

1. The effectiveness, symbols of the vaccine registration certificate, and the time limit for submitting extension registration applications for vaccines shall be implemented in accordance with the provisions of Article 8 of Circular No. 32/2018/TT-BYT.

2. Approved Vietnamese language label and user guide models may not be included in the commercial packaging of vaccines but can be published on the Drug Administration Department's electronic information website and provided to each vaccination center to ensure that healthcare staff and vaccine users have full access to approved information.

Article 8. Provisions on verifying the authenticity of information on legal documents

1. The Drug Administration Department shall cooperate with diplomatic agencies and domestic and foreign relevant agencies or through information searches on the official English-language database system provided by authorized agencies of countries to verify the authenticity of legal documents in vaccine registration applications, specifically as follows:

a) Certificate of Pharmaceutical Product (CPP) or alternative legal documents as stipulated in Point d Clause 2 Article 15 of this Circular for applications for issuance, extension, change, or addition to the vaccine registration certificate.

b) Legal documents issued by competent foreign state management agencies for foreign registration entities registering drugs in Vietnam for the first time.

2. Verification of authenticity shall be conducted concurrently with the review process of vaccine registration applications and must have results of verifying the authenticity of legal documents as specified in Clause 1 of this Article before issuing, extending, changing, or adding to the vaccine registration certificate.

Article 9. Organization and operation of the Advisory Board for issuing drug registration certificates, including drug ingredients

The organization and operation of the Advisory Board for issuing drug registration certificates, including drug ingredients, shall be carried out in accordance with the provisions of Clause 44 of Circular No. 32/2018/TT-BYT.

Article 10. Organization and operation of experts reviewing vaccine registration dossier

The organization and operation of experts reviewing vaccine registration dossier shall be carried out in accordance with the provisions of Clause 45 of Circular No. 32/2018/TT-BYT.

Chapter II

REQUIREMENTS FOR CLINICAL DATA TO ENSURE SAFETY, EFFECTIVENESS AND CRITERIA FOR DETERMINING THE CASE OF EXEMPTION FROM CERTAIN STAGES OF VACCINE CLINICAL TRIALS, VACCINES MUST UNDERGO CLINICAL TRIAL PHASE 4 IN VIETNAM

Article 11. Provisions on clinical data in the vaccine registration dossier

1. Requirements for clinical data to ensure safety and effectiveness in the vaccine registration dossier shall be implemented in accordance with points a and b of Clause 1, Article 13 of Circular No. 32/2018/TT-BYT.

2. For vaccines registered for production at a production site or facility different from that used for clinical trials, the entity must use the clinical data of the vaccine used in the clinical trials and prove that changing the production site or facility does not affect the quality standards of the vaccine. In cases where the registering entity or production facility is not the owner or not part of the same group as the owner of the clinical data, permission to use the clinical data must be obtained from the owner.

After being issued a registration certificate, the registering entity must cooperate with the production facility to continue evaluating the safety and immunogenicity of the vaccine in the target population in Vietnam during use, following the guidance of the Ministry of Health (National Institute of Medicine Science and Training) for vaccines that have not been approved for circulation by strict regulatory authorities (Strengthening Regulatory Authorities - SRA) as stipulated in Clause 10, Article 2 of Circular No. 32/2018/TT-BYT.

3. Domestic-produced COVID-19 vaccines currently undergoing clinical trials but already having interim Phase 3 results regarding the safety and protective efficacy of the vaccine based on immunogenicity data may be conditionally registered upon review by the National Bioethics Committee for Biomedical Research on the vaccine undergoing clinical trials in Vietnam and advice from the Advisory Board for issuing drug registration certificates, including drug ingredients, for each specific vaccine, taking into account guidelines or recommendations from the World Health Organization (WHO).

Vaccines granted under the above circumstances must continue to be monitored for safety and efficacy, controlled in terms of recipients, quantity, and scope of use after issuance of the registration certificate.

After obtaining approval for circulation, the registering entity must cooperate with the production facility to continue conducting clinical research and updating clinical data according to the guidance of the Ministry of Health (National Institute of Medicine Science and Training).

Article 12. Requirements for clinical data for vaccines that have been issued a registration certificate in Vietnam but have changes or supplements related to clinical data compared to the approved vaccine registration dossier

For vaccines that have been issued a registration certificate in Vietnam and have changes or supplements related to clinical data compared to the approved vaccine registration dossier, the registering entity must supplement clinical data in accordance with Appendix II attached to Circular No. 32/2018/TT-BYT or consistent with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Common Technical Document (CTD) or one of the guidelines of the United States Food and Drug Administration (USFDA), European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA) of the United Kingdom, or the World Health Organization (WHO).

Article 13. Cases Eligible for Exemption from One or Several Clinical Trial Phases when Registering for Circulation

Vaccines that have not met the requirements stipulated in Clause 1, Article 11 of this Circular shall be exempted from one or several clinical trial phases (including exemption from clinical data) by the Minister of Health based on the advisory opinion of the Advisory Council for Drug Registration upon meeting one of the following conditions:

1. The vaccine has been licensed for circulation in at least one country and has clinical safety and efficacy data.

In cases where the drug regulatory authority of the country granting circulation license does not belong to one of the regulatory authorities specified in Clause 10, Article 2 of Circular No. 32/2018/TT-BYT, after obtaining the circulation registration certificate, the applicant must cooperate with the manufacturer to continue evaluating the safety and immunogenicity in the target population in Vietnam during usage according to the guidelines of the Ministry of Health (Department of Science, Technology and Training).

2. The vaccine is produced in Vietnam through technology transfer of one, some, or all production stages of the finished product process, where the pre-transfer vaccine has clinical safety and efficacy data already licensed for circulation in at least one country.

Article 14. Cases Requiring Phase 4 Clinical Trials in Vietnam

Based on the advisory opinion of the Advisory Council for Drug Registration, vaccines that have been granted circulation registration certificates but require additional evaluation of safety and efficacy must undergo Phase 4 clinical trials in Vietnam.

Chapter III

APPLICATION FOR ISSUANCE, EXTENSION, AMENDMENT, AND SUPPLEMENTATION OF VACCINE CIRCULATION REGISTRATION CERTIFICATES

Article 15. Provisions for Documents in Applications for Issuance, Extension, Amendment, and Supplementation of Vaccine Circulation Registration Certificates

1. Documents in applications for issuance, extension, amendment, and supplementation of vaccine circulation registration certificates shall comply with the provisions of Clauses 1, 2, 3, 7, 8, 9, 10, 11, and Clause 15 of Article 23 of Circular No. 32/2018/TT-BYT and Point a and Point 1 of Clause 5 of Article 1 of Circular No. 29/2020/TT-BYT dated December 31, 2020, issued by the Minister of Health to amend, supplement, and abolish certain legal normative documents issued by the Minister of Health (hereinafter referred to as Circular No. 29/2020/TT-BYT).

2. Provisions on the Certificate of Pharmaceutical Product (CPP):

a) The CPP must bear the signature, name of the signatory, date of issue, and stamp of the issuing authority.

b) The CPP must be issued by a pharmaceutical management authority.

In cases where the CPP is issued by an authority other than a pharmaceutical management authority, the vaccine applicant must provide documentation proving that such authority is authorized and that the pharmaceutical management authority in that country does not issue CPPs as required by local law.

c) The content of the CPP must include all information as prescribed in Appendix 02 attached to this Circular. Any appendices accompanying the CPP (if any) must be confirmed by the issuing authority.

d) In cases where there is no CPP for imported vaccines, it may be replaced by legal documents issued by the competent authority of the foreign country certifying that the vaccine has been licensed for circulation, containing at minimum the following information: vaccine name, active ingredient, concentration or quantity of active ingredient, dosage form, name and address of the manufacturing facility, and confirmation that the vaccine is actually circulating in that country.

If the vaccine involves production by multiple manufacturing facilities, the CPP or replacement legal document must clearly state the name, address, and role of each facility.

3. The application form shall be implemented according to Appendix 03 attached to this Circular. Other administrative documents in the application package must be signed and stamped by the legal representative or an authorized person of the legal representative of the applicant, without using a seal signature.

4. The power of attorney shall be implemented according to Appendix 04 attached to this Circular. Each application must submit an original or certified copy of the power of attorney stamped by the applicant or the office representative's stamp (for foreign applicants) in the following cases:

a) The power of attorney named according to Appendix 04A attached to this Circular.

b) The power of attorney signed on the application form according to Appendix 04B attached to this Circular; if the authorized person signing the application is not the head of the office representative, the power of attorney must bear the stamp and signature of confirmation by the head of the office representative in Vietnam (for foreign applicants).

5. Quality standards, testing methods, test reports, and stability research files (applicable to both raw material and finished product sections) must be originals bearing the signature and stamp of confirmation by the manufacturer; in cases of submitting copies, they must be stamped by the applicant (accepting the stamp of the office representative for foreign drugs).

If the manufacturer does not use stamps as required by the local regulations, there is no requirement for a stamp of confirmation for foreign manufacturers. In this case, the applicant must stamp and confirm that the producing country does not use stamps and take responsibility for the authenticity of the documents.

The test report must include the following information: administrative information (name and address of the manufacturing facility, name and signature of the responsible person, date of the test report) and information about the vaccine sample and raw materials (product name, batch number, expiration date, quality standards applied, quality criteria, quality requirements, test results, conclusion on the quality of the batch).

Article 16. Quality Documents in the Application for Issuance, Amendment, or Supplement of Vaccine Registration Certificate

Quality documents shall be implemented in accordance with Clause 7, Article 25 of Circular No. 32/2018/TT-BYT, guided in Part II - ASEAN Common Technical Document (ACTD) or Section 3-ICH-CTD, and the following provisions:

1. The batch release certificate issued by the testing unit designated by the competent authority of the producing country.

2. In cases where the applicant cannot provide the documents stipulated in Sub-clause 1 of this Article, the applicant shall provide a test report, quality standards, and testing methods confirmed by the testing units designated by the competent authority of the producing country in accordance with Clause 5, Article 1 of Circular No. 03/2020/TT-BYT dated January 22, 2020, amending and supplementing certain articles of Circular No. 11/2018/TT-BYT dated May 4, 2018, of the Minister of Health on drug quality and raw material drug quality.

3. The dossier for assessing the production process and stability studies must include data from three commercial-scale batches.

In cases where data from three commercial-scale batches are not provided, there must be at least one commercial-scale batch and two pilot-scale batches (minimum scale being one-tenth of the commercial-scale batch), along with a comparison table of the production process and stability studies of vaccines produced at commercial scale versus pilot scale, clinical trial vaccine batches, and test reports for each corresponding batch.

4. Quality dossier for technology transfer vaccines when the pre-transfer vaccine has an existing valid registration certificate in Vietnam:

The quality dossier for technology transfer vaccines shall be carried out according to the guidelines set forth in Sub-clauses 1, 2, and 3 of this Article and the following provisions:

a) A detailed comparison table of changes and supplements (if any) between the pre-transfer vaccine and the transferred vaccine, and supporting documentation as prescribed in Appendix II attached to Circular No. 32/2018/TT-BYT and Sub-clause 2, Article 18 of this Circular;

b) Dossier of the active substance component of the transferred vaccine provided by the recipient of the technology transfer when there is a change in the manufacturing site of the active substance compared to the pre-transfer vaccine;

c) Dossier of the finished product component of the transferred vaccine, carried out by the recipient of the technology transfer, including:

- An assessment report of the production process (for production stages carried out at the recipient of the technology transfer);

- An evaluation report of the analytical procedure's suitability (which may be replaced by an analytical procedure transfer dossier jointly conducted by the transferring and receiving entities);

- Batch analysis data, Finished Product Test Report.

5. In cases where the pre-transfer vaccine has not been granted a registration certificate in Vietnam or its registration certificate has expired: the quality dossier for the transferred vaccine shall be carried out according to the guidelines set forth in Sub-clause 4 of this Article and the quality dossier of the pre-transfer vaccine according to the guidelines in Part II-ACTD or Section 3-ICH-CTD.

6. For vaccines repackaged in Vietnam

The entire quality dossier of the pre-repackaged vaccine in Vietnam shall be carried out according to the guidelines in Part II-ACTD or Section 3-ICH-CTD and Sub-clauses 1, 2, and 3 of this Article in cases where the pre-repackaged vaccine in Vietnam has not been granted a registration certificate in Vietnam or its registration certificate has expired.

Article 17. Preclinical and clinical documentation in the application for issuance, amendment, or supplementation of vaccine registration certificates

1. Preclinical documentation shall be carried out in accordance with the guidelines set forth in Part III-ACTD or Section 4-ICH-CTD.

2. Clinical documentation shall be carried out in accordance with the guidelines set forth in Part IV-ACTD or Section 5-ICH-CTD.

Article 18. Application for issuance, extension, amendment, or supplementation of vaccine registration certificates

1. The application for issuance, extension, amendment, or supplementation of vaccine registration certificates shall comply with the provisions stipulated in Clause 1, Clause 3, and Clause 4 of Article 28 of Circular No. 32/2018/TT-BYT and Articles 15 and 16 of this Circular, as well as the following documents:

a) For vaccines registered in the same application as provided for in Clause 2 of Article 5 of this Circular: Quality documentation must be fully prepared for each type of single-dose and multi-dose packaging, for each production facility involved in the production process as specified in this Circular;

b) For vaccines that change production location or production facility as provided for in Clause 2 of Article 11 of this Circular:

- Authorization letter from the owner of the clinical data allowing the production facility or the registration entity to use the clinical data when the registration entity or production facility is not the owner or does not belong to the same group as the owner of the clinical data;

- Documentation and evidence proving that changing the production location or production facility does not affect the quality standards of the vaccine.

2. In cases where the application for amendment or supplementation of content is not covered or has not been specifically defined in Appendix II issued together with Circular No. 32/2018/TT-BYT (including updates on viral strain changes), the registration entity shall classify and submit technical documents according to one of the guidelines of the USFDA, EMA, MHRA, or WHO.

Article 19. Application for issuance, extension, amendment, or supplementation of vaccine registration certificates for technology transfer and secondary packaging

1. Vaccines subject to technology transfer must meet the following requirements simultaneously:

a) Technology transfer for vaccine production must be conducted in the form of transferring technology to produce one, several, or all stages of the vaccine production process to the receiving entity for pharmaceutical production. If only secondary packaging is transferred, it shall not be considered as technology transfer for vaccine production.

b) Vaccines subject to technology transfer and vaccines prior to technology transfer must meet the following criteria simultaneously:

- Same formulation of the vaccine;

- Same production facility, same quality standards, and analytical procedures for the active ingredient;

- Same quality standards and analytical procedures for excipients used in vaccine production;

- Same quality standards, analytical procedures, and production processes for the vaccine;

c) In cases where vaccines subject to technology transfer differ from vaccines prior to technology transfer as stipulated in Point a of Clause 1 of this Article, they shall be implemented in accordance with the guidelines set forth in Appendix II issued together with Circular No. 32/2018/TT-BYT and the provisions stipulated in Clause 2 of Article 18 of this Circular.

2. Application for issuance of a registration certificate for vaccines subject to technology transfer in cases where vaccines prior to technology transfer already have valid registration certificates in Vietnam.

a) Administrative documents

Implement the provisions stipulated in Point a and Point b of Clause 1 of Article 18 of this Circular and the following documents:

- Administrative documents as stipulated in Point a of Clause 5 of Article 28 of Circular No. 32/2018/TT-BYT, excluding the Registration Form implemented according to Appendix 03 and the Authorization Letter (if applicable) implemented according to Appendix 04 issued together with this Circular;

- Certificate of Good Manufacturing Practice for the receiving entity for vaccine production with a scope of production suitable for the transferred vaccine;

- Transfer of technology registration certificate for cases of technology transfer as stipulated in Clause 1 of Article 31 of the Law on Technology Transfer;

b) Quality documentation: implement in accordance with the provisions stipulated in Clause 4 of Article 16 of this Circular;

c) Preclinical and clinical documentation: implement in accordance with the provisions stipulated in Article 17 of this Circular.

3. Application for issuance of a registration certificate for vaccines subject to technology transfer in cases where vaccines prior to technology transfer do not have registration certificates in Vietnam or their registration certificates in Vietnam have expired.

a) Administrative documents:

Implement the provisions stipulated in Point a and Point b of Clause 1 of Article 18 of this Circular and the following documents:

- Administrative documents as stipulated in Point b of Clause 5 of Article 28 of Circular No. 32/2018/TT-BYT, excluding the Registration Form implemented according to Appendix 03 and the Authorization Letter (if applicable) implemented according to Appendix 04 issued together with this Circular;

- Legal documents replacing the product certification for pharmaceutical products as stipulated in Point d of Clause 2 of Article 15 of this Circular for foreign vaccines prior to technology transfer (if applicable);

- Certificate of Good Manufacturing Practice for the receiving entity for vaccine production with a scope of production suitable for the transferred vaccine;

- Transfer of technology registration certificate for cases of technology transfer as stipulated in Clause 1 of Article 31 of the Law on Technology Transfer;

b) Quality documentation: implement in accordance with the provisions stipulated in Clause 5 of Article 16 of this Circular;

c) Preclinical and clinical documentation: implement in accordance with the provisions stipulated in Article 17 of this Circular;

d) Documentation for vaccines prior to technology transfer includes the documents of the vaccines prior to technology transfer as stipulated in the application for issuance of a registration certificate under Clause 1 of Article 18 of this Circular.

In cases where there is no application for issuance of a registration certificate for vaccines prior to technology transfer, the proposed label for circulation in Vietnam is not required.

4. Application for issuance of a registration certificate for vaccines subject to secondary packaging in Vietnam in cases where vaccines prior to secondary packaging have valid registration certificates in Vietnam: implement in accordance with the provisions stipulated for changing the secondary packaging facility in Appendix II issued together with Circular No. 32/2018/TT-BYT.

5. Application for issuance of a registration certificate for vaccines subject to secondary packaging in Vietnam in cases where vaccines prior to secondary packaging do not have registration certificates in Vietnam or their registration certificates in Vietnam have expired:

Implement the provisions stipulated in Point a and Point b of Clause 1 of Article 18 of this Circular and the following documents:

a) Administrative documents as stipulated in Point b of Clause 6 of Article 28 of Circular No. 32/2018/TT-BYT, excluding the Authorization Letter (if applicable) implemented according to Appendix 04 issued together with this Circular;

b) Quality documentation: implement in accordance with the provisions stipulated in Clause 6 of Article 16 of this Circular.

6. Application for extension, amendment, or supplementation of registration certificates for vaccines subject to technology transfer and secondary packaging in Vietnam:

The application dossier for extending, changing, or supplementing the vaccine registration certificate for technology transfer and secondary packaging shall be implemented in accordance with the provisions of Clause 3 and Clause 4 of Article 28 of Circular No. 32/2018/TT-BYT and Article 15 of this Circular. In cases where the application dossier for changes or supplements does not fall within or has not been specifically stipulated in Appendix II issued together with Circular No. 32/2018/TT-BYT (including updates on viral strain mutations), the registering entity shall submit technical documentation in accordance with one of the guidelines of the USFDA, EMA, MHRA, or the WHO.

Chapter IV

PROCEDURES FOR ISSUING, EXTENDING, CHANGING, SUPPLEMENTING, AND REVOKING VACCINE REGISTRATION CERTIFICATES

Article 20. Competence to organize assessment, issue, extend, change, and supplement vaccine registration certificates

1. The Minister of Health shall instruct the Drug Administration Department to organize the assessment of applications for issuing, extending, changing, and supplementing vaccine registration certificates and approve changes and supplements to vaccine registration certificates.

2. The Minister of Health shall authorize the Director of the Drug Administration Department to issue and extend vaccine registration certificates based on the assessment opinions of the dossier and the advisory opinions of the Advisory Council for Drug Registration and Pharmaceutical Raw Materials.

Article 21. General Provisions

1. General procedures for issuing, extending, changing, and supplementing vaccine registration certificates shall be carried out in accordance with the provisions of Article 37 of Circular No. 32/2018/TT-BYT.

2. For missing documents in the registration dossier as stipulated in Articles 18 and 19 of this Circular at the time of submission, the registering entity may continue to update them during the dossier assessment process and must complete them before the issuance of the registration certificate. The updating period of the dossier by the registering entity shall not be included in the assessment period specified in Clause 1 of Article 22 of this Circular.

Article 22. Procedures for Issuing Vaccine Registration Certificates

1. Within a maximum period of 20 working days from the date of receipt of all necessary documents for applications for issuing vaccine registration certificates, the Director of the Drug Administration Department shall issue the vaccine registration certificate. If the certificate is not issued or not issued yet, the Drug Administration Department shall notify in writing and specify the reasons. The processing times for each step are as follows:

a) Within two working days from the date of receiving the dossier, the Drug Administration Department shall send the dossier to the legal expert for administrative dossier assessment, the National Institute of Vaccines and Medical Biological Products for quality dossier assessment, and the Clinical Pharmacology Center of Hanoi Medical University for pharmacological and clinical dossier assessment. Within seven working days from the date of receiving the dossier from the Drug Administration Department, the experts and assessment units must complete the assessment records and submit them to the Drug Administration Department for consolidation and recommendation on the assessment record.

b) Within three working days from the date of receiving the assessment record, the Drug Administration Department shall notify in writing for dossiers that have not met the requirements and specify the reasons. For dossiers proposed for issuance, non-issuance, or requiring further assessment and advisory opinions of the Advisory Council for Drug Registration and Pharmaceutical Raw Materials, the Drug Administration Department shall transfer them to the Council Office for a meeting of the Advisory Council or seek written opinions from Council members.

c) Within two working days from the date of receiving materials from the Drug Administration Department, the Council Office shall convene a meeting of the Advisory Council for Drug Registration and Pharmaceutical Raw Materials or seek written opinions from Council members.

d) Within three working days from the date of the Council meeting, the Council Office shall complete the Council meeting record and transfer it to the Drug Administration Department.

đ) Within three working days from the date of receiving the Council meeting record, the Director of the Drug Administration Department shall decide to issue the registration certificate for dossiers that meet the requirements; the Drug Administration Department shall notify in writing according to the Council's conclusion for dossiers that have not met the requirements, not met, and specify the reasons.

2. For supplementary requests in the notification of the Drug Administration Department, the registering entity must submit supplementary materials within 36 months for cases requiring preclinical and clinical data, stability study data, or within 12 months for other supplementary materials, from the date of the Drug Administration Department's notification. After this period, if the registering entity does not submit supplementary materials, the submitted dossier will lose its validity.

The registering entity shall notify the Drug Administration Department in writing of any updated information related to the safety and efficacy of the vaccine compared to the submitted dossier and currently under assessment.

The period from the date of the Drug Administration Department's notification to the date the registering entity submits supplementary materials shall not be counted towards the deadline specified in Clause 1 of this Article.

3. Within 15 working days from the date of receipt of all supplementary materials, the Director of the Drug Administration Department shall decide to issue the registration certificate for dossiers that meet the requirements; the Drug Administration Department shall notify in writing according to the Advisory Council's conclusion for dossiers that have not met the requirements, not met, and specify the reasons.

The procedure for reviewing supplementary materials shall be carried out in accordance with the provisions of Clause 1 of this Article.

4. In cases where multiple production entities participate in implementing one or several production stages or the entire production stages of a vaccine registered in the same dossier as stipulated in Clause 2 of Article 5 of this Circular, a single registration certificate shall be issued.

Article 23. Procedure for Extending the Vaccine Circulation Registration Certificate

1. Within 18 working days from the date of receiving complete files, the Director of the Drug Administration Department shall extend the vaccine circulation registration certificate. In cases where extension is not granted or has not been granted, the Drug Administration Department shall issue a notification document and specify the reasons. The timeframes for each step are specified as follows:

a) Within two working days from the date of receiving complete files, the Drug Administration Department shall conduct a review, classify, and send the file to the legal expert for administrative file assessment, and the Clinical Pharmacology Center of Hanoi Medical University for pharmacological file assessment. Within five working days from the date of receiving the file from the Drug Administration Department, the experts and assessing units must complete the assessment record and submit it to the Drug Administration Department for consolidation and recommendation on the assessment record;

b) Within three working days from the date of receiving the assessment record, the Drug Administration Department shall issue a notification document for incomplete assessment files and specify the reasons. For files proposed for extension by the Drug Administration Department, non-extension, or requiring consultation from the Advisory Council for Drug Registration and Raw Material Registration, the Drug Administration Department shall transfer the file to the Council Office for a meeting with the Advisory Council for Drug Registration and Raw Material Registration or request opinions from Council members in writing;

c) Within two working days from the date of receiving materials from the Drug Administration Department, the Council Office shall convene a meeting of the Advisory Council for Drug Registration and Pharmaceutical Raw Materials or seek written opinions from Council members.

d) Within three working days from the date of the Council meeting, the Council Office shall complete the Council meeting record and transfer it to the Drug Administration Department.

d) Within three working days from the date of receiving the meeting record of the Advisory Council for Drug Registration and Raw Material Registration, the Director of the Drug Administration Department shall decide to extend the circulation registration certificate for files that meet the requirements. The Drug Administration Department shall issue a notification document according to the Council's conclusion for incomplete assessment files, non-compliant files, and specify the reasons.

2. For additional requirements stated in the notification document of the Drug Administration Department, within twelve months from the date the Drug Administration Department issues the notification document, the registration entity must submit supplementary materials as required. After this period, if the registration entity does not submit supplementary materials, the submitted file will lose its validity.

The registration entity shall notify the Drug Administration Department in writing of any updated information related to the safety and efficacy of the drug compared to the previously submitted file and currently under assessment.

The period from the date of the Drug Administration Department's notification to the date the registering entity submits supplementary materials shall not be counted towards the deadline specified in Clause 1 of this Article.

3. Within eighteen working days from the date of receiving complete supplementary materials, the Director of the Drug Administration Department shall decide to extend the circulation registration certificate for files that meet the requirements. The Drug Administration Department shall issue a notification document according to the Advisory Council's conclusion for incomplete assessment files, non-compliant files, and specify the reasons.

The procedure for reviewing supplementary materials shall be carried out in accordance with the provisions of Clause 1 of this Article.

Article 24. Procedure for Changing and Supplementing the Vaccine Circulation Registration Certificate During the Validity Period of the Registration Certificate

1. Changing and supplementing the vaccine circulation registration certificate for significant changes in indications, dosage, and target population.

Within fourteen working days from the date of receiving complete files, the Drug Administration Department shall approve significant changes in indications, dosage, and target population. In cases where approval is not granted or has not been granted, the Drug Administration Department shall issue a notification document and specify the reasons. The timeframes for each step are specified as follows:

a) Within two working days from the date of receiving complete files, the Drug Administration Department shall send the file to the legal expert for administrative file assessment, the National Institute of Vaccines and Biologicals for quality file assessment, and the Clinical Pharmacology Center of Hanoi Medical University for pharmacological and clinical file assessment. Within five working days from the date of receiving the file from the Drug Administration Department, the experts and assessing units must complete the assessment record and submit it to the Drug Administration Department for consolidation and recommendation on the assessment record;

b) Within two working days from the date of receiving the assessment record of the sub-committees, the Drug Administration Department shall issue a notification document for incomplete assessment files and specify the reasons. For files that meet the requirements or other cases requiring consultation from the Advisory Council for Drug Registration and Raw Material Registration, the Drug Administration Department shall transfer the file to the Council Office for a meeting with the Advisory Council for Drug Registration and Raw Material Registration or request opinions from Council members in writing.

c) Within two working days from the date of the Council meeting, the Council Office shall complete the meeting record and transfer it to the Drug Administration Department;

d) Within three working days from the date of receiving the meeting record of the Advisory Council for Drug Registration and Raw Material Registration, the Drug Administration Department shall approve changes and supplements for files that meet the requirements; issue a notification document according to the Council's conclusion for incomplete assessment files, non-compliant files, and specify the reasons.

2. Changing and supplementing the vaccine circulation registration certificate, except for the cases stipulated in Clause 1 and Clause 3 of this Article:

Within ten working days from the date of receiving complete files, the Drug Administration Department shall approve changes and supplements. In cases where approval is not granted or has not been granted, the Drug Administration Department shall issue a notification document and specify the reasons. The timeframes for each step are specified as follows:

a) Within two days from the date of receiving complete files, the Drug Administration Department shall send the file to the legal expert for administrative file assessment and the assessing units including the National Institute of Vaccines and Biologicals for quality file assessment, and the Clinical Pharmacology Center of Hanoi Medical University for pharmacological and clinical file assessment. Within five working days from the date of receiving the file from the Drug Administration Department, the experts and assessing units must complete the assessment record and submit it to the Drug Administration Department for consolidation and recommendation on the assessment record;

b) Within three working days from the date of receiving the assessment record of the sub-committees, the Drug Administration Department shall approve changes and supplements for the circulation registration certificate for files that meet the requirements; issue a notification document for incomplete assessment files, non-compliant files, and specify the reasons.

3. For minor changes that only require notification (Notification), amend and supplement the vaccine registration certificate as follows:

Pursuant to point đ, clause 5, Article 1 of Circular No. 29/2020/TT-BYT.

4. In cases where the Drug Administration requires additional information in its notification, the applicant must submit the required supplementary materials within 36 months for preclinical and clinical data, stability research data, or within 12 months for other supplementary data, from the date of receipt of the notification from the Drug Administration. If the supplementary materials are not submitted within this period, the previously submitted application will lose its validity.

The registering entity shall notify the Drug Administration Department in writing of any updated information related to the safety and efficacy of the vaccine compared to the submitted dossier and currently under assessment.

The period from the date of the Drug Administration Department's notification to the date the registering entity submits supplementary materials shall not be counted towards the deadline specified in Clause 1 of this Article.

5. Within seven working days from the date of receiving all supplementary materials for applications under clause 1 of this Article, five working days from the date of receiving all supplementary materials for applications under clause 2 of this Article, and three working days from the date of receiving all supplementary materials for applications under clause 3 of this Article, the Drug Administration shall approve the amendment and supplementation of the vaccine registration certificate for applications meeting the requirements; notify the applicants for applications that do not meet the requirements, specifying the reasons.

The procedure for reviewing supplementary materials shall be carried out in accordance with the provisions of clauses 1 and 2 of this Article.

6. The time limit for implementing amendments and supplements to the vaccine registration certificate shall not exceed twelve months from the date the Drug Administration issues the approval document, except in cases where the Drug Administration has different requirements.

7. Vaccine registration entities and vaccine manufacturing entities shall update the label and instructions for use of vaccines on their own without submitting an application or notifying the Drug Administration for the following changes and supplements:

a) Implementing the labeling of vaccines, vaccine raw materials, and instructions for use of vaccines as stipulated in clause 2, Article 35 of Circular No. 01/2018/TT-BYT dated January 18, 2018, issued by the Minister of Health regarding drug labeling, raw material labeling for drugs, and drug instruction sheets (hereinafter referred to as Circular No. 01/2018/TT-BYT);

b) Implementing changes and supplements to the content of labels and instructions for use of vaccines in accordance with the content specified in the Drug Administration's request;

c) Except for situations where samples of labels and instructions for use of vaccines must be resubmitted upon changes and supplements as prescribed in Appendix II attached to Circular No. 32/2018/TT-BYT, other changes related to information on labels and instructions for use of vaccines must be updated by the registration entity and manufacturer after approval by the Drug Administration for these changes and supplements;

d) Other contents:

- Changing the information about the importing entity of vaccines or raw materials for vaccines on the label or instruction sheet;

- Correcting typographical errors on the label or instruction sheet;

- Changing the layout of sections in the instruction sheet without altering the approved content of the instruction sheet;

- Supplementing quality standards information on the label and instruction sheet according to the approved application;

- Changes and supplements in accordance with the Drug Administration's notification regarding the review results of the vaccine registration application.

Article 25. Documents, Procedures, Competent Authorities, and Revocation of Vaccine Circulation Registration Certificates

Documents, procedures, competent authorities, and revocation of vaccine circulation registration certificates shall be carried out in accordance with the provisions set forth in Article 42 of Circular No. 32/2018/TT-BYT.

Chapter V

IMPLEMENTING PROVISIONS

Article 26. Effective date

This Circular takes effect from the date of signature until December 31, 2022.

Article 27. Transitional Provisions

1. For vaccine circulation registration applications submitted to the receiving authority before this Circular takes effect but are still under processing, relevant provisions of this Circular shall apply in a manner that facilitates businesses, organizations, and individuals.

2. In cases where this Circular expires and there is no replacement document or extension of its implementation period:

a) For applications for issuance, extension, change, or supplementation of vaccine circulation registration certificates during the validity period of such certificates, the entity must submit the application in accordance with Circular No. 32/2018/TT-BYT;

b) For vaccine registration applications submitted in accordance with this Circular but not yet issued with a circulation registration certificate, the applicant must continue to supplement the application in accordance with Circular No. 32/2018/TT-BYT;

c) For imported vaccine batches delivered at the port of export country before January 1, 2023, the label model and user guide shall continue to comply with the provisions of Clause 2, Article 7 of this Circular.

Imported vaccine batches delivered at the port of the exporting country after December 31, 2022, shall comply strictly with the provisions of Circular No. 01/2018/TT-BYT regarding the label model and user guide.

Article 28. Cross-references

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 29. Responsibility for Implementation

1. The Drug Administration Department shall be responsible for:

a) Organize and implement the provisions of this Circular;

b) Update the content of the label and user guide of vaccines within five working days from the date of issuance, extension, change, or supplementation of the circulation registration certificate and other registration information on the website of the Drug Administration Department;

c) Within two days from the date of issuance, extension, change, or supplementation of the circulation registration certificate, the Drug Administration Department shall return the label and user guide of the vaccine to the applicant and publish the approved label and guide on its website;

d) Develop, issue, and organize the implementation of standard operating procedures (SOPs) for vaccine registration in accordance with the provisions of this Circular.

đ) In cases where the registration entity, production entity, or related entities are found to have engaged in fraudulent behavior or unauthorized modification of documents, records, or legal papers of Vietnamese or foreign authorities; using counterfeit seals or forging signatures or stamps of the registration entity, production entity, and related entities in the registration dossier, the Drug Administration Department shall handle the matter according to the provisions of Point d and đ, Clause 1, Article 58 of the Medicine Law and the provisions of Clause 2, Clause 3, and Clause 4, Article 100 of Decree No. 54/2007/NĐ-CP dated May 8, 2017, of the Government detailing certain provisions and measures for implementing the Medicine Law.

In addition to the above measures, the Drug Administration Department shall publicize the violation details on its website and simultaneously notify the inspection agency and other competent authorities to consider and handle the matter in accordance with the law;

e) When necessary, the Drug Administration Department shall convene meetings with the registration entity, production entity, and review experts to clarify issues related to the review of the vaccine registration dossier.

2. The Science, Technology, and Training Department shall be responsible for:

a) Serving as the lead in directing, guiding the implementation, organizing the review, evaluation, and acceptance of clinical trial results of domestically produced vaccines conducted before and after the issuance of the circulation registration certificate; and the safety and immunogenicity test results on target populations in Vietnam for vaccines produced abroad as stipulated;

b) Notifying the Drug Administration Department of the acceptance results of national ethical review boards for clinical trials of vaccines conducted before and after the issuance of the circulation registration certificate.

3. The Preventive Medicine Department shall be responsible for:

a) Incorporating training and monitoring of facilities using vaccines into the vaccination process to ensure healthcare workers use vaccines in accordance with the approved user guide;

b) Receiving, evaluating, and summarizing information related to adverse events following immunization (AEFI);

c) Sharing information about severe post-vaccination adverse events with the Drug Administration Department as required;

d) Serving as the lead in guiding and controlling the target population, quantity, and scope of vaccine usage during circulation as specified in Clause 3, Article 11 of this Circular.

4. The National Institute of Vaccines and Biologicals shall be responsible for:

a) Organizing the review of the dossier and sending the review results and related professional recommendations concerning the quality section (if applicable) to the Drug Administration Department for consolidation;

b) Ensuring confidentiality of information related to the dossier in accordance with current regulations;

c) Cooperating with the production and import entities to conduct quality testing of COVID-19 vaccines before they are put into use in accordance with current regulations.

5. The Clinical Pharmacology Center of Hanoi Medical University shall be responsible for:

a) Organizing the review of the dossier and sending the review results and related professional recommendations concerning the pharmacological and clinical sections (if applicable) to the Drug Administration Department for consolidation;

b) Ensuring confidentiality of information related to the dossier in accordance with current regulations.

6. The National DI & ADR Center shall be responsible for:

a) Receiving and summarizing information related to adverse events following immunization (AEFI) and reporting to the Preventive Medicine Department;

b) Receiving and summarizing safety and efficacy reports on vaccines from pharmaceutical business entities and reporting to the Drug Administration Department, the Preventive Medicine Department, and related units.

7. Provincial Health Departments shall be responsible for inspecting and auditing the implementation of this Circular by pharmaceutical production and trading entities within their jurisdiction.

8. Entities under the Ministry of Health, Vietnam Pharmaceutical Corporation (VNP), and vaccine trading entities shall be responsible for implementing this Circular.

9. Vaccination facilities must establish vaccination procedures, train, and supervise healthcare staff to ensure that vaccines are used in accordance with the approved procedures and have full access to all information contained in the Vietnamese user guide approved by the Drug Administration Department.

10. Importing entities shall cooperate with registering entities to provide samples of labels and the Vietnamese user guide, which have been approved, to vaccination facilities.

During the implementation process, if there are difficulties or obstacles, agencies, organizations, and individuals should reflect them to the Ministry of Health (Drug Administration Department) for consideration and resolution./.