DECISION

PROMULGATING GUIDELINES FOR COVID-19 VACCINE RESEARCH, CLINICAL TRIALS, MARKETING AUTHORIZATION AND USE

MINISTER OF HEALTH

Pursuant to the Law on Prevention and Control of Infectious Diseases No. 03/2007/QH12 dated 21/11/2007;

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

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

Pursuant to the Government's Decree No. 54/2017/ND-CP dated May 08, 2017 elaborating Law on Pharmacy;

Pursuant to the Government’s Decree No. 104/2016/ND-CP dated July 01, 2016 on vaccination;

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Pursuant to the Circular No. 32/2018/TT-BYT dated November 12, 2018 by the Minister of Health on marketing authorization of drugs and medicinal ingredients;

Pursuant to the Circular No. 35/2018/TT-BYT dated November 22, 2018 by the Minister of Health on Good Manufacturing Practices for pharmaceutical products and pharmaceutical starting materials;

At the request of the Director General of Administration of Science Technology and Training, Director General of Drug Administration of Vietnam and Director General of General Department of Preventive Medicine of the Ministry of Health.

HEREBY DECIDES:

Article 1. Promulgated together with this Decision are the guidelines for COVID-19 vaccine research, clinical trials, marketing authorization and use.

The guidelines for COVID-19 vaccine research, clinical trials, marketing authorization and use promulgated together with this Decision are applicable during the COVID-19 pandemic.

Article 2. This Decision takes effect from the date on which it is signed.

Article 3. Director General of Administration of Science Technology and Training, Director General of Drug Administration of Vietnam, Director General of General Department of Preventive Medicine, Head of Office of the Ministry of Health, heads of relevant regulatory bodies and organizations, and relevant individuals shall implement this Decision./.

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P.P. THE MINISTER
THE DEPUTY MINISTER




Tran Van Thuan

GUIDELINES

FOR COVID-19 VACCINE RESEARCH, CLINICAL TRIALS, MARKETING AUTHORIZATION AND USE

Section 1. VACCINE RESEARCH AND QUALITY CONTROL

Article 1. Research on COVID-19 vaccines

1. Every COVID-19 vaccine must undergo preclinical assessment of its safety, immunogenicity and ability to protect animal models from challenge, which shall be carried out by its manufacturer.

2. The manufacturer shall provide sufficient vaccine samples, typical chemicals and documents according to regulations for National Institute for Control of Vaccine and Biologicals to inspect the quality of its vaccine and certify that the vaccine meets quality requirements.

Article 2. Inspection of quality of vaccine batches undergoing clinical trial

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2. National Institute for Control of Vaccine and Biologicals shall conduct new tests and regular tests necessary for COVID-19 vaccine quality control on its premises or assign officials to conduct these tests independently/concurrently on the premises of the manufacturer or supervise the testing procedures of the manufacturer to ensure that these tests are carried out in an accurate, scientific and impartial manner.

Section 2. VACCINE CLINICAL TRIALS

Article 3. General regulations on COVID-19 vaccine clinical trials

1. Clinical trial procedures, requirements for language, presentation and legality of documents, and organization of clinical trials are provided for in Articles 18, 20 and 24 of the Circular No. 29/2018/TT-BYT dated October 29, 2018 by the Minister of Health on clinical trial of drugs (hereinafter referred to as “Circular No. 29/2018/TT-BYT”).

2. Rights and responsibilities of the sponsor, the institution, investigators and the principal investigator as well as rights and obligations of clinical trial participants are provided for in Articles 3, 4, 5, 6 and 7 of the Circular No. 10/2020/TT-BYT dated June 11, 2020 by the Minister of Health on bioequivalence studies for drugs (hereinafter referred to as “Circular No. 10/2020/TT-BYT”).

3. Conducting of clinical trials, recording, reporting, statistical analysis, monitoring and supervision, and audit of clinical trials, remedial actions for adverse events, reporting of adverse events in clinical trials in Vietnam, finance and remuneration for trial participants, clinical trial termination, and reporting and announcement of clinical trial results are provided for in Articles 13, 17, 18, 19, 20, 21, 22 and 23 of the Appendix enclosed with Circular No. 10/2020/TT-BYT.

Article 4. Documents required for COVID-19 vaccine clinical trials

1. Application for permission for clinical trial, which is prepared in compliance with regulations in Clause 1 Article 19 of Circular No. 29/2018/TT-BYT.

2. Application for approval for clinical trial, which is prepared according to regulations in Clause 2 Article 19 of Circular No. 29/2018/TT-BYT and documents about the clinical trial in previous phases (mentioned in Point b Clause 2 Article 19 of Circular No. 29/2018/TT-BYT) included in which shall be prepared as follows:

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b) Application for permission for phase 2 of the clinical trial may use results of interim assessment of the safety and immunogenicity (if any) of phase 1 instead of results of assessment of the whole phase 1 while phase 1 is not yet completed.

c) Application for permission for phase 3 of the clinical trial may use results of interim assessment of the safety and immunogenicity (if any) of phase 2 instead of results of assessment of the whole phase 2 while phase 2 is not yet completed.

3. Application for approval for change to clinical trial, which is prepared in compliance with regulations in Clause 3 Article 19 of Circular No. 29/2018/TT-BYT.

4. Application for approval for clinical trial results, which is prepared in compliance with regulations in Clause 4 Article 19 of Circular No. 29/2018/TT-BYT.

Article 5. Clinical trial application procedure

Procedure for application for permission to conduct a COVID-19 vaccine clinical trial is provided for in Article 21 of Circular No. 29/2018/TT-BYT.

Article 6. Protocol approval and clinical trial result approval

1. Procedures for protocol approval, approval for amendment to protocol and approval for results of COVID-19 vaccine clinical trials are provided for in Articles 22, 23 and 25 of Circular No. 29/2018/TT-BYT.

2. The national research ethics committee shall validate the applications in emergency meetings according to regulations in Article 26 of Circular No. 04/2020/TT- BYT dated March 05, 2020 by the Minister of Health on establishment, functions, tasks and rights of research ethics committees.

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Article 7. Clinical trial protocol

Clinical trial protocol is provided for in Article 8 of the Appendix enclosed with Circular No.10/2020/TT-BYT.

Article 8. Clinical trial design

Clinical trial design is provided for in Article 9 of the Appendix enclosed with Circular No.10/2020/TT-BYT, in which:

1. Phase 1 may be designed as an independent trial or together with phase 2 in one protocol. Phase 2 may be designed together with phase 3 in one protocol.

2. Phase 1 may be conducted in one or more than one center; phase 2 shall be a double-blind, randomized comparison study conducted at one or more than one center; phase 3 shall be a double-blind, randomized comparison study conducted at multiple centers.

3. The protocol must specify the standards applied to the interim assessment results if these results are used to consider transitioning to the following phase or apply for marketing authorization following the emergency procedure applicable to vaccines against pandemics.

4. In case Vietnam does not have sufficient COVID-19 cases to design vaccine efficacy assessment (phase 3, case-based assessment), a study may be designed to compare the immunogenicity of the vaccine in question with that of a vaccine which belongs to a country with a WHO-recognized national regulatory authority (NRA) and the efficacy assessment results of which are available.

Article 9. Sample size is provided for in Article 10 of the Appendix of Circular No. 10/2020/TT-BYT, in which, recommended total sample size of phase 1 is 30-150 subjects. Recommended minimum total sample size of phase 2 used for result analysis is 200 subjects. Recommended minimum total sample size of phase 3 used for result analysis is 800 subjects. In case of phase 3 study for assessment of a vaccine’s protection effectiveness, minimum total sample size shall be 800 subjects, who must be monitored for at least 01 year after the date of administration of the last dose.

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Article 11. Technical documents and quality control for clinical trials are provided for in Clause 1 Article 15 of the Appendix of Circular No. 10/2020/TT-BYT.

Article 12. Technical standards for personnel are provided for in Article 16 of the Appendix of Circular No. 10/2020/TT-BYT, excluding the regulation restricting every principal investigator from taking charge of more than 03 clinical trials at the same time.

Section 3. ASSESSMENT OF COMPLIANCE WITH GMP REQUIREMENTS

Article 13. Compliance with GMP requirements of domestic COVID-19 vaccine production lines shall be directly assessed according to regulations of Circular No. 35/2018/TT-BYT dated 22/11/2018 by the Minister of Health on Good Manufacturing Practices for pharmaceutical products and pharmaceutical starting materials (hereinafter referred to as “Circular No. 35/2018/TT-BYT”) for the purpose of granting of registration numbers.

Article 14. Compliance with GMP requirements of overseas COVID-19 vaccine production facilities shall be assessed according to regulations of the Government’s Decree No. 54/2017/ND-CP dated 08/5/2017 on guidelines for implementation of Law on Pharmacy (hereinafter referred to as “Decree No. 54/2017/ND-CP”).

Section 4. MARKETING AUTHORIZATION

Article 15. Drug Administration of Vietnam shall submit a report to the marketing authorization advisory council, which will provide the basis for the marketing authorization advisory council to consider and approve use of phase 1 and phase 2 results and results of interim assessment of phase 3 of safety and immunogenicity for application for marketing authorization based on validation of documents on safety and efficacy by validation specialists. Based on opinions of the marketing authorization advisory council, Drug Administration of Vietnam shall submit a report to the Minister of Health, which will provide the basis for the Minister of Health to consider and decide to exempt one or more than one clinical trial phase according to regulations in Clause 1 Article 18 of Circular No. 32/2018/TT-BYT dated 12/11/2018 by the Minister of Health on marketing authorization of drugs and medicinal ingredients (hereinafter referred to as “Circular No. 32/2018/TT-BYT”).

Article 16. Applications for issuance, renewal and revision of marketing authorization for COVID-19 vaccines are provided for in Articles 23, 24, 25, 26, 27 and 28 of Circular No. 32/2018/TT-BYT, including the following documents, which require much time for preparation:

- Test report, specifications and test method certified by National Institute for Control of Vaccine and Biologicals, which may be added after results are available.

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- Data on clinical trial results, which may be updated during the application validation process.

Article 17. Marketing authorization for a COVID-19 vaccine shall be granted following the simplified procedures provided for in Article 41 of Circular No. 32/2018/TT-BYT to shorten the procedure while ensuring the safety, quality and efficacy of the vaccine based on benefit/risk analysis.

Section 5. VACCINE USE AND IMPLEMENTING RESPONSIBILITY

Article 18. COVID-19 vaccines shall be prioritized for localities and individuals facing high risk as appropriate to real-world situation and vaccine provision capacity.

Article 19. General Department of Preventive Medicine shall take charge and cooperate with Drug Administration of Vietnam, Department of Planning and Finance and relevant departments of the Ministry of Health, Institutes of Hygiene and Epidemiology, Pasteur Institutes and relevant units in formulating and proposing plans for COVID-19 vaccine receipt, preservation, distribution and use to Ministry leaders for consideration and approval.

Article 20. Implementing responsibilities

1. Administration of Science Technology and Training shall:

a) Provide guidance on implementation of these Guidelines and monitor such implementation.

b) Act as the body in charge of receiving and processing applications for permission for COVID-19 vaccine clinical trial, approving and carrying out commissioning of COVID-19 vaccine clinical trials according to Circular No. 29/2018/TT-BYT as soon as practicable.

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2. Drug Administration of Vietnam shall organize assessment of compliance with GMP requirements of COVID-19 vaccine production lines according to Decree No. 54/2017/ND-CP and Circular No. 35/2018/TT-BYT as soon as practicable; and organize validation of applications for COVID-19 vaccine marketing authorization according to Circular No. 32/2018/TT-BYT as soon as practicable.

3. General Department of Preventive Medicine shall formulate a plan for use of authorized COVID-19 vaccines and supervision of vaccine reactions.

4. National Institute for Control of Vaccine and Biologicals shall inspect quality of COVID-19 vaccines to ensure quality of vaccines used in clinical trials, ensure that vaccines are registered as soon as practicable and exercise after-sales supervision of vaccines granted marketing authorization.

5. National Institute of Hygiene and Epidemiology, Pasteur Institute of Ho Chi Minh City, Pasteur Institute of Nha Trang and Vietnam Military Medical University shall cooperate with and assist vaccine manufacturers in COVID-19 vaccine research, manufacturing and clinical trials as soon as practicable.

6. The national research ethics committee and internal research ethics committees shall carry out validation and commissioning of applications for permission for COVID-19 vaccine clinical trial as soon as practicable; and monitor and inspect COVID-19 vaccine clinical trials to ensure the safety of trial participants and the accuracy and trustworthiness of research data.

7. Organizations and individuals involved in COVID-19 vaccine research and manufacturing shall comply with these guidelines and relevant laws during COVID-19 vaccine clinical trial, marketing authorization and use processes.