Circular No. 29/2018/TT-BYT promulgates the Circular on clinical drug trials.

CIRCULAR

Regulations on Clinical Drug Trials

Pursuant to Law No. 105/2016/QH13 dated April 6, 2016 on pharmaceuticals;

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

At the proposal of the Director of the Science, Technology and Training Department, Ministry of Health;

The Minister of Health issues this Circular on Clinical Drug Trials.

PART I
GENERAL PROVISIONS

Article 1. Scope of Regulation

1. This Circular stipulates the issuance and application of Good Clinical Practice (GCP) for clinical drug trials; evaluation of compliance with Good Clinical Practice for clinical drug trials and clinical trial files and procedures.

2. Activities related to clinical drug trials that involve medical examination and treatment must comply not only with the provisions of this Circular but also with the laws on medical examination and treatment.

Article 2. Applicability

This Circular applies to:

1. Clinical drug trial facilities include:

a) Clinical drug trial service business establishments are those businesses certified to have the necessary conditions for pharmaceutical business operations within the scope of clinical drug trials.

b) Pharmaceutical bioequivalence testing service business establishments are those businesses certified to have the necessary conditions for pharmaceutical business operations within the scope of pharmaceutical bioequivalence testing.

c) Establishments not subject to certification under Clause 1, Article 35 of the Medicine Law, including medical examination and treatment establishments, scientific research establishments conducting clinical drug trials and bioequivalence testing of drugs without commercial purposes, and other establishments conducting such activities without commercial purposes.

Organizations and individuals involved in clinical drug trial activities.

Article 3. Explanation of Terms

1. Clinical drug trial is a scientific study of drugs on voluntary subjects aimed at investigating or determining the safety and efficacy of the drug; identifying and detecting adverse reactions caused by the drug; the ability to absorb, distribute, metabolize, and eliminate the drug.

2. Good Clinical Practice (GCP) is a set of principles and standards for designing, implementing, conducting, monitoring, inspecting, recording, analyzing, and reporting clinical drug trials to ensure the reliability and accuracy of data and research results reports, and to protect the rights, safety, and confidentiality of information of research subjects.

3. International regulations on clinical drug trials recognized by the Ministry of Healthinclude the Guidelines on Good Clinical Practice specified in the Common Technical Document for Registration of Pharmaceuticals for Human Use (ICH), the World Health Organization's (WHO) Good Clinical Practice Guidelines, and other guidelines on clinical drug trials from reference regulatory authorities as stipulated in Clause 5 of this Article.

4. Investigator’s Brochure (IB) is a document containing preclinical and clinical trial information and data of the investigational drug.

5. Reference Regulatory Authority referred to in this Circular includes: European Medicines Agency (EMA), United States, Japan, France, Germany, Sweden, United Kingdom, Switzerland, Australia, Canada, Belgium, Austria, Ireland, Denmark, and Netherlands.

6. Case Report Form (CRF) is a paper or electronic tool designed to collect research data from participants in clinical drug trials.

Chapter II
ISSUANCE AND APPLICATION GOOD CLINICAL PRACTICE FOR CLINICAL DRUG TRIALS

Article 4. Principles and Standards for Good Clinical Practice (GCP) in Clinical Drug Trials

1. Enact principles and standards for Good Clinical Practice (GCP) in clinical drug trials as set out in Appendix I attached to this Circular and update relevant regulations based on the guidance from ICH, WHO, and other reference regulatory authorities as stipulated in Clause 5, Article 3 of this Circular.

2. In case ICH and WHO amend or supplement the GCP principles and standards (updated documents), the Science, Technology and Training Department shall update and publish these updated documents on the Ministry of Health's electronic portal and the Science, Technology and Training Department's electronic portal for related parties to consult, update, and apply.

Article 5. Subjects Applying Principles and Standards for Good Clinical Practice (GCP) in Clinical Drug Trials

1. Clinical trial sites must implement and comply with the GCP principles and standards as set out in Appendix I attached to this Circular and updated documents.

2. In cases where biological equivalent testing service business establishments and establishments conducting non-commercial biological equivalent testing services for drugs do not meet the GCP requirements for the clinical research phase, they must enter into contracts or cooperation agreements with clinical trial sites that meet the GCP requirements as set out in Appendix I attached to this Circular and updated documents to carry out the clinical research phase.

3. Clinical trial sites must apply updated GCP documents according to the provisions of Clause 2, Article 4 of this Circular within 12 months if there is a requirement for changes in infrastructure serving drug trials, or within six months for other updates, calculated from the date the updated documents are published by the Science, Technology and Training Department on the Ministry of Health's electronic portal and the Science, Technology and Training Department's electronic portal.

Chapter III
GENERAL PROVISIONS ON ASSESSING COMPLIANCE GOOD CLINICAL PRACTICE FOR CLINICAL DRUG TRIALS

Article 6. Circumstances for Assessing, Inspecting, and Monitoring Compliance with Good Clinical Practice (GCP)

1. The initial assessment is conducted concurrently with the issuance of the certificate of eligibility for operating drug testing service businesses and biological equivalent testing service businesses for drugs (hereinafter referred to as drug testing service business establishments). For clinical trial sites specified in Point c, Clause 1, Article 2 of this Circular, the initial assessment is carried out when the site commences clinical drug trial activities.

2. Periodic assessments to maintain compliance with GCP are conducted every three years from the date of signing the evaluation report of the previous assessment (excluding any surprise inspections, audits, and checks by the Ministry of Health and Provincial Health Departments).

3. Surprise assessments to verify compliance with GCP are conducted as stipulated in Clause 1, Article 15 of this Circular.

4. Inspection and monitoring activities to ensure ongoing compliance with GCP at clinical trial sites are carried out in accordance with laws governing inspection and monitoring.

Article 7. Levels of Compliance with Good Clinical Practice (GCP)

The assessment of compliance with GCP at clinical trial sites is conducted at three levels as follows:

1. Level 1: The clinical trial site complies with GCP without any issues requiring rectification or correction.

2. Level 2: The clinical trial site has issues that need to be rectified or corrected to comply with GCP, provided that such issues do not affect the quality of research and the safety and health of trial participants.

3. Level 3: The clinical trial site does not comply with GCP in the following circumstances:

a) There are discrepancies with GCP standards that pose a risk to the quality of research and/or the health and safety of trial participants.

b) Fraud, forgery, alteration of data, records, and documents.

Chapter IV
INITIAL ASSESSMENT OF COMPLIANCE WITH GOOD CLINICAL PRACTICE (GCP) IN CLINICAL DRUG TRIALS

Article 8. Documents for Initial Evaluation of Compliance with Good Clinical Practice for Testing Medicines

1. The documents serving as the basis for evaluating compliance with GCP for business entities providing drug testing services are the application documents for obtaining a certificate of eligibility to operate in pharmaceuticals (submitted when applying for a certificate of eligibility to operate in pharmaceuticals, business entities providing drug testing services do not need to submit additional documents) as stipulated in Article 38 of the Medicine Law and Article 32 of Decree No. 54/2017/NĐ-CP dated May 8, 2017 of the Government detailing certain provisions and measures to implement the Medicine Law (hereinafter referred to as Decree No. 54/2017/NĐ-CP). In cases where business entities providing drug testing services must comply with special supervision as prescribed in Article 38 of the Medicine Law and Article 49 of Decree No. 54/2017/NĐ-CP;

For technical documents on business entities providing drug testing services as prescribed in Article 38 of the Medicine Law and Article 32 of Decree No. 54/2017/NĐ-CP, these documents should be presented according to the overall dossier guidelines set out in Appendix II attached hereto or an updated overall dossier if there is an expansion of scope of activities, bearing the stamp of the business entity providing drug testing services.

If a business entity providing drug testing services applies for both a GCP certification and a certificate of eligibility to operate in pharmaceuticals, the business entity must clearly state this in the Application for Certificate of Eligibility to Operate in Pharmaceuticals.

2. The documents serving as the basis for evaluating compliance with GCP for clinical trial sites as specified in point c, Clause 1, Article 2 of this Circular include:

a) An application for evaluation of compliance with GCP according to Form No. 01 prescribed in Appendix III attached hereto. If the entity applies for a GCP certification, it must clearly state this in the application;

b) Technical documents on the site presented according to the overall dossier guidelines set out in Appendix II attached hereto, bearing the stamp of the entity.

Article 9. Procedure for Receiving Documents for Evaluation of Compliance with Good Clinical Practice for Testing Medicines

1. Receiving documents:

a) Business entities providing clinical trial services for medicines and other entities conducting non-commercial clinical trials for medicines shall submit one set of documents as prescribed in Article 8 of this Circular along with the review fee as stipulated by the Minister of Finance regarding the review fee for standards and conditions for clinical trials for medicines to the Department of Science, Technology and Training, Ministry of Health.

b) Business entities providing bioequivalence testing services for medicines and other entities conducting non-commercial bioequivalence testing for medicines shall submit one set of documents including all required documents as prescribed in Article 8 of this Circular along with the review fee as stipulated by the Minister of Finance regarding the review fee for standards and conditions for bioequivalence testing for medicines to the Drug Administration Department, Ministry of Health. The Drug Administration Department will act as the focal point for receiving documents and coordinate with the Department of Science, Technology and Training to organize the evaluation of compliance with good clinical practice for testing medicines.

2. The procedure for receiving and reviewing documents shall be implemented in accordance with the provisions of:

a) Clauses 2, 3, 4, 5, and 6 of Article 50 of Decree No. 54/2017/NĐ-CP for clinical trial sites for narcotic drugs, psychotropic drugs, precursor substances, raw materials for narcotic drugs, psychotropic drugs, precursors used for making drugs, radioactive drugs; combination drugs containing narcotic substances, combination drugs containing psychotropic substances, combination drugs containing precursors;

b) Clauses 2, 3, 4, and 5 of Article 51 of Decree No. 54/2017/NĐ-CP for clinical trial sites for toxic drugs, raw materials for toxic drugs; drugs, drug substances listed in the list of prohibited substances for use in certain sectors and fields;

c) Clauses 2, 4, and 5 of Article 33 of Decree No. 54/2017/NĐ-CP for entities not covered by the cases specified in points a and b above.

3. Within five working days from the date of receipt of complete documents, the Department of Science, Technology and Training or the Drug Administration Department (hereinafter referred to as the Receiving Authority) shall establish an Evaluation Team (hereinafter referred to as the Evaluation Team), notify the clinical trial site in writing about the Evaluation Team and the anticipated time for on-site evaluation.

Within fifteen days from the date of the notification, the Evaluation Team shall conduct on-site evaluation at the entity in accordance with the provisions of Article 10 of this Circular.

Article 10. Procedure for evaluating compliance with Good Clinical Practice (GCP)

1. Evaluation procedure:

a) Step 1. The evaluation team announces the Decision on the establishment of the evaluation team; the purpose, content, and plan of the evaluation at the clinical trial site.

b) Step 2. The clinical trial site provides a summary of its organizational structure, personnel, activities implemented, application of GCP, or other issues relevant to the evaluation content.

c) Step 3. The evaluation team conducts an actual assessment of the implementation and application of GCP at the clinical trial site according to each specific evaluation content.

d) Step 4. The evaluation team meets with the clinical trial site to inform about the level of compliance with GCP of the clinical trial site as stipulated in Article 7 of this Circular, non-compliant contents, necessary corrections and improvements identified during the evaluation (if any); discusses with the clinical trial site in cases where the site does not agree with the evaluation of the team on each content.

e) Step 5. Draft and sign the evaluation minutes

The evaluation minutes are signed and confirmed by the Head of the clinical trial site and the Head of the evaluation team; the minutes must reflect the composition of the evaluation team, location, time, scope of the evaluation, and unresolved issues (if any) between the evaluation team and the clinical trial site related to the evaluation of GCP compliance. The minutes are prepared in three copies: one copy retained at the clinical trial site, two copies retained at the Receiving Authority.

2. Report on the evaluation of GCP compliance

a) Immediately after completing the actual evaluation at the clinical trial site, the evaluation team is responsible for preparing the Report on the Evaluation of GCP Compliance according to Form No. 02 prescribed in Appendix III issued together with this Circular, listing and analyzing in detail the non-compliant contents that the clinical trial site needs to correct and improve (if any), comparing with the corresponding provisions of legal documents, and assessing the degree of compliance with GCP of the clinical trial site as stipulated in Article 7 of this Circular.

b) In case the clinical trial site disagrees with the evaluation content, within thirty days from the date of signing the evaluation minutes, the clinical trial site shall submit a written explanation to the Receiving Authority along with evidence (document files, images, videos, certificates) proving the matter related to the evaluation content.

c) Within ten days from the date of receiving the written explanation from the clinical trial site, the Receiving Authority will review the GCP report and the explanation of the clinical trial site, seek expert advice in relevant fields (if necessary), and issue a written response to the clinical trial site. The response must clearly state the acceptance or non-acceptance of the explanation of the clinical trial site. This period is not included in the evaluation deadline.

Article 11. Handling the Results of Evaluating Compliance with Good Clinical Practice

1. In case the report on the evaluation of GCP compliance concludes that the clinical trial site complies with GCP as stipulated in Clause 1 of Article 7 of this Circular:

Within ten working days from the date of signing the evaluation minutes, the Receiving Authority shall submit to the Minister of Health for issuance of a certificate of eligibility for pharmaceutical business operations and issue a certificate of GCP compliance according to Form No. 03 prescribed in Appendix III issued together with this Circular if the site has requested it in the application for a certificate of eligibility for pharmaceutical business operations. If the site does not request a GCP compliance certificate, the report on the evaluation of GCP compliance concluding that the clinical trial site complies with GCP shall be valid as a certificate of GCP compliance for the clinical trial site and can be used as a basis for submitting to the Minister of Health for issuance of a certificate of eligibility for pharmaceutical business operations or as a basis for conducting clinical trials for the clinical trial sites specified in Point c, Clause 1 of Article 2 of this Circular.

In case the clinical trial site conducts drug testing and special control drug sales, within twenty days from the date of completion of the actual evaluation at the clinical trial site and signing the evaluation minutes, if the site requests it in the application, the Receiving Authority shall issue a certificate of GCP compliance according to Form No. 03 prescribed in Appendix III issued together with this Circular (simultaneously with issuing the certificate of eligibility for pharmaceutical business operations).

2. In case the report on the evaluation of GCP compliance concludes that the clinical trial site needs to correct and improve as stipulated in Clause 2 of Article 7 of this Circular:

a) Within five working days from the date of completion of the actual evaluation at the clinical trial site and signing the evaluation minutes, the Receiving Authority shall send the report on the evaluation of GCP compliance along with a notification of the contents that need correction and improvement to the clinical trial site.

In case the clinical trial site conducts drug testing and special control drug sales, within fifteen days from the date of completion of the actual evaluation at the clinical trial site and signing the evaluation minutes, the Receiving Authority shall send the report on the evaluation of GCP compliance along with a notification of the contents that need correction and improvement to the clinical trial site.

b) After completing the correction and improvement, the clinical trial site must submit a written report along with evidence (document files, images, videos, certificates) proving the completion of the correction and improvement of the contents recorded in the evaluation report.

c) Within twenty days from the date of receipt of the correction and improvement report from the clinical trial site, the Receiving Authority will review the correction report of the clinical trial site and conclude on the compliance status of the clinical trial site:

- In case the correction and improvement of the clinical trial site meet the requirements: The Receiving Authority shall proceed as stipulated in Clause 1 of this Article.

- In case the remediation and repair of the clinical trial testing facility do not meet the requirements: The agency receiving the application shall issue a document requesting continued remediation and repair until the requirements are met.

d) Within six months from the date the agency receiving the application issues a document requesting remediation and repair, the clinical trial testing facility must submit a remediation and repair report according to the request. After this period, if the clinical trial testing facility does not remediate or repair, or if within twelve months from the date of the first submission of the application, the remediation and repair report does not meet the requirements, then the submitted application will lose its validity.

3. In the case where the report on the assessment of compliance with Good Clinical Practice (GCP) concludes that the clinical trial testing facility does not comply with GCP as stipulated in Clause 3, Article 7 of this Circular:

Within five working days from the date of completing the actual assessment at the clinical trial testing facility and signing the assessment record, the agency receiving the application shall issue a notification regarding non-compliance with GCP, attaching the GCP assessment report to the clinical trial testing facility and not issuing a certificate of GCP compliance.

4. Within five working days from the date of issuance of the certificate of eligibility for pharmaceutical business operations or the certificate of GCP compliance, the agency receiving the application shall publish on the Ministry of Health's electronic portal and the agency’s website the following information:

a) Name and address of the clinical trial testing facility complying with GCP;

b) Full name of the person responsible for professional matters and their practice license number;

c) Number of the certificate of eligibility for pharmaceutical business operations and the number of the GCP compliance certificate (if applicable);

d) Expiry date of the GCP compliance evaluation and the date of the next periodic review;

đ) Scope of activities of the clinical trial testing facility.

Chapter V
ASSESSMENT OF MAINTENANCE OF COMPLIANCE GOOD CLINICAL PRACTICE FOR CLINICAL DRUG TRIALS

Article 12. Periodic Assessment of Maintenance of Compliance with Good Clinical Practice

1. Every year in November, the agency receiving the application shall announce on its website the plan for the periodic assessment of maintenance of GCP compliance for clinical trial testing facilities in the following year and send a copy of this plan to all clinical trial testing facilities listed in the plan.

2. Based on the announced periodic assessment plan, the clinical trial testing facility shall submit the application for periodic assessment in accordance with Clause 6 of this Article, accompanied by the examination fee as prescribed by the Minister of Finance for the agency receiving the application, at least thirty days before the scheduled assessment date announced by the agency receiving the application.

3. If the clinical trial testing facility fails to submit the application for periodic assessment within fifteen days from the due date, the agency receiving the application shall issue a document requesting the facility to submit the application in accordance with the regulations.

4. Within forty-five days from the date the agency receiving the application issues the document requesting submission, the clinical trial testing facility must submit the application along with an explanation for the delay in submitting the application as prescribed.

5. After submitting the application for periodic assessment of maintenance of GCP compliance within the specified time frame, the clinical trial testing facility may continue to conduct clinical trials within the scope defined in the certificate of eligibility for pharmaceutical business operations or the GCP compliance certificate for the clinical trial testing facility as stipulated in Point c, Clause 1, Article 2 of this Circular, from the date of submission of the application until the results of the periodic assessment are available.

6. The application for periodic assessment of maintenance of GCP compliance includes:

a) A request form for periodic assessment of maintenance of GCP compliance according to Form No. 04 prescribed in Appendix III attached to this Circular;

b) A summary report on the clinical trial testing activities of the clinical trial testing facility over the last three years from the date of the previous assessment (excluding any special assessments, inspections, or audits conducted by the Ministry of Health or the Department of Health) up to the date of the periodic assessment request.

c) Updated technical documentation on the physical conditions, technical capabilities, and personnel of the clinical trial testing facility (if there have been changes);

7. The procedures for handling the results of the periodic assessment of maintenance of GCP compliance shall be carried out in accordance with Articles 9, 10, and 13 of this Circular.

Article 13. Handling the Results of Periodic Evaluation on Maintaining Compliance with Good Clinical Practice (GCP)

1. In case the GCP evaluation report concludes that the clinical trial site complies with GCP as stipulated in Clause 1, Article 7 of this Circular:

Within ten days from the date of completion of the actual evaluation at the clinical trial site and signing of the evaluation record, the Receiving Authority shall issue a certificate of compliance with GCP according to Form No. 03 attached as Appendix III of this Circular if the site requests it; if the site does not request issuance of such a certificate, the GCP compliance evaluation report concluding that the clinical trial site complies with GCP shall be deemed as a certification of compliance with GCP for the clinical trial site and serve as a basis for the clinical trial site to continue conducting clinical trials.

2. In case the GCP evaluation report concludes that the clinical trial site needs to rectify and correct deficiencies as stipulated in Clause 2, Article 7 of this Circular:

a) Within five working days from the date of completion of the actual evaluation at the clinical trial site and signing of the evaluation record, the Receiving Authority shall issue a written notice requiring the clinical trial site to rectify and correct deficiencies and submit a rectification report to the Receiving Authority;

b) Within forty-five days from the date the Receiving Authority issues the written notice, the clinical trial site must complete rectification and correction and submit a written report accompanied by evidence (documentary files, images, videos, certificates) proving that the deficiencies recorded in the evaluation report have been completed;

c) Within twenty days from the date of receipt of the rectification report accompanied by evidence (documentary files, images, videos, certificates), the Receiving Authority shall evaluate the results of rectification by the clinical trial site and conclude on the status of GCP compliance of the clinical trial site as follows:

- If the rectification by the clinical trial site meets the requirements: The Receiving Authority shall issue a certificate of compliance with GCP according to Form No. 03 stipulated in Appendix III attached to this Circular;

- If the rectification by the clinical trial site does not meet the requirements: The Receiving Authority shall issue a written notice specifying the contents that need further rectification and correction and submit a supplementary report. The extended period for continued rectification and correction and reporting is forty-five days from the date of the written notice.

d) Within ninety days from the date of completion of the actual evaluation at the clinical trial site without a rectification report or after rectification as specified in Point c of this Clause but the rectification results still fail to meet the requirements, the Receiving Authority shall issue a notification regarding non-compliance with GCP and, depending on the nature and severity of the violation, the Receiving Authority shall implement one or more measures as stipulated in Points a and b of Clause 3 of this Article.

3. In case the GCP evaluation report concludes that the clinical trial site does not comply with GCP as stipulated in Clause 3, Article 7 of this Circular:

Within five working days from the date of completion of the evaluation at the clinical trial site and signing of the evaluation record, based on the assessment of risks associated with the quality of research, health, and safety of participants discovered during the evaluation, the Receiving Authority shall issue a notification regarding non-compliance with GCP and, depending on the nature and severity of the violation, the Receiving Authority shall implement one or more of the following measures:

a) Imposing administrative penalties within its authority (if applicable) or recommending the competent authority to impose administrative penalties according to the laws on handling administrative violations;

b) Submitting a proposal to the Minister of Health to issue a decision revoking the business license for pharmaceuticals already issued and/or implementing the revocation of the certificate of compliance with GCP (if any) according to Article 40 of the Drug Law.

4. Within five working days from the date of conclusion that the clinical trial site maintains compliance with GCP or from the date of issuance of the Decision to revoke the business license for pharmaceuticals already issued due to the service provider failing to maintain compliance with GCP, the Receiving Authority shall update on the Electronic Information Website of the Receiving Authority the status of GCP compliance of the clinical trial site according to the provisions of Clause 4, Article 11 of this Circular for the clinical trial site complying with GCP or information about the revocation of the business license for pharmaceuticals, certificate of compliance with GCP (if any) already issued for the service provider failing to maintain compliance with GCP.

Article 14. Control of Changes

1. During the period between periodic evaluations, clinical trial sites must implement procedures to request issuance of a business license for pharmaceuticals in accordance with point b, Clause 1, Article 36 of the Drug Law or submit an application for Good Clinical Practice (GCP) compliance assessment or a change report according to Form No. 05 prescribed in Appendix III issued together with this Circular if they fall under any of the following circumstances:

a) Change in accordance with any of the circumstances stipulated in point b, Clause 1, Article 36 of the Drug Law;

b) Change in the location of clinical trial sites as specified in point c, Clause 1, Article 2 of this Circular;

c) Change in the position of one of the technical rooms within the clinical trial laboratory (consultation room, treatment room, emergency room, laboratory, phase 1 clinical trial area) at the same business/testing location;

d) Addition of one of the technical rooms within the clinical trial laboratory (consultation room, treatment room, emergency room, laboratory, phase 1 clinical trial area) at a new position at the same business/testing location;

đ) Expansion of one of the technical rooms within the clinical trial laboratory (consultation room, treatment room, emergency room, laboratory, phase 1 clinical trial area) based on the existing room structure;

e) Repair, major structural changes, or rearrangement within one of the technical rooms within the clinical trial laboratory (consultation room, treatment room, emergency room, laboratory, phase 1 clinical trial area).

2. In cases where a clinical trial service provider undergoes changes as stipulated in point a, Clause 1 of this Article, the clinical trial service provider must submit an application for issuance of a business license for pharmaceuticals in accordance with Clauses 2 and 4, Article 38 of the Drug Law.

The process of evaluating GCP compliance, classifying results, and handling evaluation results regarding GCP compliance level shall be carried out in accordance with Articles 9, 10, and 11 of this Circular.

3. In cases where a clinical trial site as specified in point c, Clause 1, Article 2 of this Circular undergoes changes as stipulated in point b, Clause 1 of this Article, the site must submit an application for GCP compliance assessment in accordance with Clause 2, Article 8 of this Circular.

The process of evaluating GCP compliance, classifying results, and handling evaluation results regarding GCP compliance level shall be carried out in accordance with Articles 9, 10, and 11 of this Circular.

4. In cases where a clinical trial site undergoes changes as stipulated in points c and d, Clause 1 of this Article, the clinical trial site must submit a change report along with corresponding technical documentation to the Receiving Authority.

a) The Receiving Authority conducts an on-site evaluation at the clinical trial site. If the clinical trial site meets the requirements, the Receiving Authority issues a document agreeing to the change made by the clinical trial site;

b) The process of evaluating, classifying results, and handling evaluation results for clinical trial sites undergoing changes as stipulated in point c, Clause 1 of this Article shall be carried out in accordance with Articles 9, 10, and 13 of this Circular;

c) The process of evaluating, classifying results, and handling evaluation results for clinical trial sites undergoing changes as stipulated in point d, Clause 1 of this Article shall be carried out in accordance with Articles 9, 10, and 11 of this Circular.

5. In cases where a clinical trial site undergoes changes as stipulated in points đ and e, Clause 1 of this Article, the clinical trial site must submit a change report along with corresponding technical documentation to the Receiving Authority. The Receiving Authority evaluates the change report submitted by the clinical trial site.

a) Within 10 days from the date of receiving the notification letter, the Receiving Authority issues a notification letter agreeing to the change content if the change meets the requirements;

b) Within 10 days from the date of receiving the notification letter, the Receiving Authority issues a notification letter specifying the necessary corrections and repairs if the requirements are not met;

c) Within 45 days from the date the Receiving Authority issues the notification letter, the clinical trial site must complete the corrections and repairs and issue a notification letter accompanied by evidence (documentary files, images, videos, certificates) proving that the identified deficiencies have been corrected;

d) Within 10 days from the date of receiving the correction report accompanied by evidence (documentary files, images, videos, certificates), the Receiving Authority evaluates the correction results of the clinical trial site and concludes on the GCP compliance status of the clinical trial site:

- If the corrections meet the requirements: The Receiving Authority issues a notification letter agreeing to the change content;

- If the corrections do not meet the requirements: The Receiving Authority conducts an urgent evaluation and handles the evaluation results in accordance with Article 15 of this Circular.

Article 15. Sudden Assessment of Compliance with Good Clinical Practice for Clinical Drug Trials

1. Upon request from the Ministry of Health or the Department of Health, based on the level of risk to the health of trial participants posed by the drug being tested, and the degree of compliance with GCP as stipulated in Article 7 of this Circular, the Receiving Authority shall conduct a sudden assessment of GCP compliance at clinical trial sites in any of the following cases:

a) The clinical trial site has not yet met the requirements set forth in point d, Clause 5, Article 14 of this Circular;

b) A clinical trial site that complies with Level 2 GCP as defined in Clause 2, Article 7 of this Circular must be subject to at least one sudden assessment within three years from the end date of the previous assessment period;

c) The clinical trial site has been found to have serious violations of GCP principles and standards through inspection reports issued by competent authorities;

d) There is information reflecting or recommending that the clinical trial site has seriously violated GCP principles and standards;

đ) The clinical trial site fails to submit the application for GCP compliance maintenance assessment as required under Clause 4, Article 12 of this Circular.

2. The composition of the Assessment Team shall be decided by the Director of the Receiving Authority based on the scope and purpose of the assessment.

3. The procedures and processes for conducting sudden assessments at clinical trial sites shall be carried out according to the provisions of Clauses 6 and 7, Article 12 of this Circular.

Chapter VI
ASSESSMENT TEAM FOR COMPLIANCE GOOD CLINICAL PRACTICE FOR CLINICAL DRUG TRIALS

Article 16. Composition and Standards for Members of the Assessment Team

1. The Minister of Health decides to establish the Assessment Team for GCP Compliance, which includes the following members:

a) One representative from the leadership of the Receiving Authority serving as the Head of the Team;

b) One clerk from the Receiving Authority serving as the Secretary of the Team;

c) Representatives from units under the Ministry of Health (each unit may have a maximum of one member), including: the Department of Medical Examination and Treatment; the Legal Affairs Department; the National Bioethics Council for Biomedical Research; the Department of Medicines; the Department of Science, Technology and Training; the Department of Traditional Medicine Management in the case of a clinical trial site dealing with herbal medicine or traditional medicine services;

d) One member representing the Department of Health of the province or centrally-administered city (hereinafter referred to as the Department of Health) where the main office of the clinical trial site is located, in the case of a site under the jurisdiction of the Department of Health;

đ) Other relevant agency or unit members when necessary.

2. Staff participating in the Evaluation Team must meet the following standards:

a) Having a bachelor’s degree or higher;

b) Having received training on GCP and GCP assessment;

c) Being honest, impartial, and strictly adhering to regulations and laws during the assessment process without conflicts of interest with the clinical trial service provider being assessed as stipulated in Clause 3 of this Article;

d) The Head of the Team must hold a bachelor's degree in medicine or pharmacy and have at least five years of experience in managing clinical trials.

3. Conflict of Interest Evaluation Principle: A member of the Assessment Team shall be considered to have a conflict of interest with the clinical trial site being assessed if they fall into any of the following situations:

a) They have worked for the clinical trial site being assessed within the last five years;

b) They have participated in advisory activities for the clinical trial site being assessed within the last five years;

c) They currently have financial interests with the clinical trial site being assessed;

d) Their spouse, children, parents, siblings, or relatives of their parents, spouse, or children are employed by the clinical trial site being assessed.

Article 17. Responsibilities and Authorities of the Evaluation Team

1. Responsibilities of the Inspection Team:

a) Evaluate the entire clinical trial activity of the clinical trial site according to the Good Clinical Practice (GCP) stipulated in Article 4 of this Circular, updated GCP documents (if any), and related technical regulations; specifically record the evaluation contents, identified issues, prepare minutes, and report on the evaluation;

b) Prepare or explain the GCP evaluation result report in cases where the clinical trial site disagrees with the content of the Report;

c) Maintain confidentiality over all information related to the evaluation period and all information related to the clinical trial activities of the clinical trial site; except when there is consent from the clinical trial site or upon request from competent state authorities for inspection, supervision, or investigation purposes.

2. Authorities of the Inspection Team:

a) Inspect all areas relevant to the clinical trial activities of the clinical trial site;

b) Request the provision of documents and materials related to the clinical trial activities of the clinical trial site;

c) Collect evidence documentation (photocopies of documents, photographs, videos) that prove the issues discovered during the evaluation process;

d) Prepare minutes and require the clinical trial site to temporarily suspend clinical trial activities if the Evaluation Team discovers serious violations affecting the safety and health of clinical trial participants or the accuracy and integrity of research data during the evaluation process, and report to the competent authority for handling according to regulations.

Chapter VII
CLINICAL TRIAL FILES AND PROCEDURES

Article 18. Clinical Trial Procedures

Clinical trials include stages and procedures carried out in accordance with Articles 86 and 95 of the Drug Law and are specified as follows:

1. Registration of clinical trial research;

2. Approval of clinical trial research including initial approval and changes during the implementation of clinical trials when the clinical trial site makes changes to the clinical trial research outline or participant informed consent forms;

3. Organization of clinical trial implementation;

4. Approval of clinical trial results.

Article 19. Clinical Trial Files

Clinical trial files include registration research application files; research approval application files; change approval application files; and result approval application files, which are specified as follows:

1. Clinical trial research registration file includes:

a) A clinical trial research registration form according to Model No. 06 prescribed in Appendix III issued together with this Circular;

b) Product information file (general information about the drug under clinical trial: name, components, indications, physical and chemical properties, formulation, and other related information); preclinical research documents; previous phase clinical trial research documents, in Vietnamese or English with a Vietnamese summary attached.

2. Clinical trial research approval application file includes:

a) A clinical trial research approval application form according to Model No. 07 prescribed in Appendix III issued together with this Circular;

b) Drug information file including:

- Drug research documents: formula composition, production process, quality standards, drug testing certificates (for chemical drugs, herbal medicines, traditional medicines: testing certificates from state drug testing facilities meeting Good Laboratory Practice (GLP) standards or private drug testing service providers meeting GLP standards suitable for their scope of operations or manufacturers meeting Good Manufacturing Practice (GMP) standards; for vaccines: quality testing certificates from national certification agencies or release certificates for vaccine batches);

- Preclinical research documents of the drug to be tested: reports on pharmacological effects, toxicity, safety, dosage recommendations, administration routes, usage methods;

- Previous phase clinical trial research documents (if applying for subsequent phase clinical trials and the drug does not fall within the category exempted from previous phases);

c) Legal documents of the drug under clinical trial including:

- A copy of the registration research approval document from the Department of Science, Technology and Training, Ministry of Health;

- A certified copy or stamped copy from the entity presenting the original for comparison of the document requesting Phase 4 clinical trials from the competent drug management agency for drugs applying for Phase 4 clinical trials;

- The approved drug usage guide for drugs applying for Phase 4 clinical trials;

- A certified copy or stamped copy from the entity presenting the original for comparison of the business operation permit certificate for drug testing service providers;

- Confirmation letters from participating organizations for multi-center studies in Vietnam;

- A certified copy or stamped copy from the entity presenting the original for comparison of the approval document from the People's Committee of provinces or centrally administered cities for field studies;

- Clinical trial research cooperation contracts between entities, organizations, or individuals with the drug under trial and clinical trial service providers; cooperation contracts between entities or individuals with the drug under trial and research support organizations (if applicable);

d) Clinical trial research outline and explanatory documents including:

- An explanation of the clinical trial research outline according to Model No. 08 prescribed in Appendix III issued together with this Circular;

- Research information collection forms or Research Case Reports (CRF);

d) Scientific curriculum vitae and a copy of the certificate of completion of the Good Clinical Practice (GCP) training course for the principal investigator issued by the Ministry of Health or by institutions authorized to train on GCP;

e) Information provision form and the informed consent form of the clinical trial subjects according to Form No. 09 prescribed in Appendix III attached hereto;

g) Minutes of the scientific and ethical review by the Institutional Review Board (IRB) at the facility level;

h) Clinical trial drug labels in accordance with Circular No. 01/2018/TT-BYT dated January 18, 2018, issued by the Minister of Health, regarding labeling of drugs, raw materials for drugs, and drug usage instructions;

3. The application dossier for approval of changes in clinical trial research includes:

a) Application form for approval of changes in clinical trial research according to Form No. 10 prescribed in Appendix III attached hereto;

b) Updated versions of corresponding documents stipulated in Clause 2 of this Article that have been changed;

c) Minutes of the IRB's review at the facility level for changes in clinical trial research that significantly affect the health and rights of participants or impact the design, procedures, and processes of the research;

4. The application dossier for approval of clinical trial results includes:

a) Application form for approval of clinical trial results according to Form No. 11 prescribed in Appendix III attached hereto;

b) Copy of the approved research protocol;

c) Copy of the Decision approving the research protocol;

d) Minutes of the IRB's review of clinical trial results at the facility level;

đ) Full report of clinical trial research results according to Form No. 12 prescribed in Appendix III attached hereto;

Article 20. Requirements for Language, Format, and Legal Validity of Dossiers

1. Language of the Dossier:

Clinical trial dossiers must be written in Vietnamese or English. In cases where they cannot be presented in Vietnamese or English, there must be a notarized translation of the document into Vietnamese or English (including consular certification and legalization);

2. Format of the Dossier:

Clinical trial dossiers must be prepared on A4 paper size, securely bound, with a table of contents, and documents arranged in the correct sequence as per the table of contents, with clear separation and guidance between sections, and each section must be numbered in order for easy reference;

3. Legal Validity of the Dossier:

a) The registration application and the content of the registration dossiers must be signed and stamped by the legal representative or the duly authorized person of the registering entity in accordance with the regulations;

b) Documents issued by foreign authorities must be legalized in accordance with the laws on consular legalization, except in cases exempted under the law;

Article 21. Procedures and Sequence for Registering Clinical Trial Research

1. Organizations or individuals with clinical trial drugs shall submit directly or through postal service one set of the clinical trial research registration dossier to the Science, Technology and Training Department, Ministry of Health;

2. Within five working days from the date of receipt of the dossier, the Science, Technology and Training Department, Ministry of Health, shall check the validity of the dossier. If the dossier is invalid, a written notice with specific guidance for supplementation until the dossier becomes valid must be issued;

3. Organizations or individuals with clinical trial drugs are responsible for cooperating with the Science, Technology and Training Department, Ministry of Health, to complete the dossier within a maximum period of sixty days from the date of receipt of the written notice. Beyond this deadline, the submitted dossier will lose its validity;

4. Within five working days from the date of receiving all valid dossiers, the Director of the Science, Technology and Training Department shall issue a written approval for clinical trial research according to Form No. 13 prescribed in Appendix III attached hereto. In case of non-approval, a written response with specific reasons must be provided.

Article 22. Procedures and sequence for approving clinical drug trial research

1. The clinical drug trial facility shall directly submit or send via postal service one set of the application dossier for approval of clinical drug trial research to the Science, Technology and Training Department of the Ministry of Health.

2. Within five working days from the date of receipt of the dossier, the Science, Technology and Training Department of the Ministry of Health shall check the validity of the dossier. In case the dossier is not valid, there must be a specific notification and guidance for the facility to supplement the dossier until it becomes valid.

The clinical drug trial facility is responsible for coordinating with the Science, Technology and Training Department of the Ministry of Health to complete the dossier within a maximum period of sixty days from the date of receipt of the notification letter. Beyond this deadline, the approval procedure for the research must be restarted from the beginning.

3. Within twenty-five days from the date of receiving a complete and valid dossier, the Ministry of Health shall convene the National Bioethics Council (hereinafter referred to as the National Bioethics Council) and issue minutes of the review of the clinical drug trial research outline.

4. Within five working days from the date of issuance of the National Bioethics Council's review minutes, the Science, Technology and Training Department shall compile and complete the dossier and submit it to the Minister of Health for decision on approval of the clinical drug trial research outline if the research outline meets the requirements. In case the research outline is not approved or requires modification, the Science, Technology and Training Department shall notify the facility in writing and specify the reasons.

5. In case the clinical drug trial research outline needs modification, the clinical drug trial facility is responsible for coordinating with the Science, Technology and Training Department of the Ministry of Health to complete the dossier within a maximum period of ninety days from the date of receipt of the notification letter. Beyond this deadline, the approval procedure for the research outline must be restarted from the beginning.

6. Within five working days from the date of receipt of the completed research outline according to the notification letter, the Science, Technology and Training Department of the Ministry of Health shall compile and complete the dossier and submit it to the Minister of Health for decision on approval of the clinical drug trial research outline.

Article 23. Procedures and sequence for approving changes to the clinical drug trial research outline

1. The clinical drug trial facility shall directly submit or send via postal service one set of the application dossier for approval of changes to the clinical drug trial research outline to the Science, Technology and Training Department of the Ministry of Health.

2. Within five working days from the date of receipt of the dossier, the Science, Technology and Training Department of the Ministry of Health shall check the validity of the dossier. In case the dossier is not valid, there must be a specific notification and guidance for the facility to supplement the dossier until it becomes valid.

The clinical drug trial facility is responsible for coordinating with the Science, Technology and Training Department of the Ministry of Health to complete the dossier within a maximum period of sixty days from the date of receipt of the notification letter. Beyond this deadline, the approval procedure for the research must be restarted from the beginning.

3. Within twenty-five days from the date of receiving a complete and valid dossier, the Ministry of Health shall convene the National Bioethics Council and issue minutes of the review of changes to the clinical drug trial research outline.

4. Within five working days from the date of issuance of the National Bioethics Council's review minutes, the Science, Technology and Training Department shall compile and complete the dossier and submit it to the Minister of Health for decision on approval of modifications and supplements to the clinical drug trial research outline if the research outline meets the requirements. In case the research outline is not approved or requires modification, the Science, Technology and Training Department shall notify the facility in writing and specify the reasons.

5. In case the clinical drug trial research outline needs modification, the clinical drug trial facility is responsible for coordinating with the Science, Technology and Training Department of the Ministry of Health to complete the dossier within a maximum period of ninety days from the date of receipt of the notification letter. Beyond this deadline, the approval procedure for the research outline must be restarted from the beginning.

6. Within five working days from the date of receipt of the completed research outline according to the notification letter, the Science, Technology and Training Department of the Ministry of Health shall compile and complete the dossier and submit it to the Minister of Health for decision on approval of modifications and supplements to the clinical drug trial research outline.

Article 24. Organization to conduct clinical drug trials

The clinical drug trial facility shall organize the implementation of clinical drug trials according to the research protocol that has been approved and the GCP guidelines.

Article 25. Procedures and sequence for approving the results of clinical drug trials

1. The clinical drug trial facility shall directly send or send via postal service one set of the application dossier for approval of the results of clinical drug trials in Vietnamese to the Science, Technology and Training Department, Ministry of Health.

2. Within five working days from the date of receipt of the dossier, the Science, Technology and Training Department of the Ministry of Health shall check the validity of the dossier. In case the dossier is not valid, there must be a specific notification and guidance for the facility to supplement the dossier until it becomes valid.

The clinical drug trial facility is responsible for coordinating with the Science, Technology and Training Department, Ministry of Health to complete the dossier within a maximum period of 60 days from the date of receipt of the notification document. Beyond this deadline, the procedure for approving the results of clinical drug trials must be restarted from the beginning.

3. Within 25 days from the date of receiving a complete and valid dossier, the Ministry of Health shall convene the National Ethics Council meeting and issue a record of acceptance of the clinical drug trial research which must include conclusions on whether the requirements are met, met but requiring corrections, supplements, or not met.

4. Within five working days from the date of having the record of acceptance meeting the safety and efficacy requirements of the National Ethics Council, the Director of the Science, Technology and Training Department shall decide to approve the results of clinical drug trials according to Model No. 14 stipulated in Appendix III issued together with this Circular. In case the record of acceptance meets the requirements but requires corrections, supplements, or does not meet the safety and efficacy requirements, the Science, Technology and Training Department shall notify the facility in writing and specify the reasons.

5. In case the record of acceptance meets the requirements but requires corrections, supplements, the facility is responsible for coordinating with the Science, Technology and Training Department, Ministry of Health to complete the dossier within a maximum period of 90 days from the date of receipt of the notification document. Beyond this deadline, the procedure for approving the results of clinical drug trials must be restarted from the beginning.

6. Within five working days from the date of receiving the completed dossier according to the notification document, the Director of the Science, Technology and Training Department shall decide to approve the results of clinical drug trials.

Chapter VIII
IMPLEMENTING PROVISIONS

Article 26. Effective date

1. This Circular shall take effect from January 1, 2019.

2. Repeal Article 2, Article 3, Article 4, Chapter III, Chapter IV, Chapter V, Chapter VI, Chapter VII, Chapter VIII, Article 39, Article 40 of Circular No. 03/2012/TT-BYT dated February 2, 2012 of the Minister of Health guiding clinical drug trials and Decision No. 799/QĐ-BYT dated March 7, 2008 of the Minister of Health on issuing "Good Clinical Practice Guidelines" from the effective date of this Circular.

Article 27. Cross-referencing Provisions

In case the referenced documents in this Circular are replaced or amended, they shall be applied according to the replaced or amended documents.

Article 28. Transitional Provisions

Dossiers submitted before the effective date of this Circular shall be reviewed and evaluated according to Circular No. 03/2012/TT-BYT dated February 2, 2012 of the Minister of Health guiding clinical drug trials or according to the provisions of this Circular if the facility requests.

Article 29. Implementation Organization

1. The Science, Technology and Training Department, Ministry of Health shall be responsible for:

a) Serving as the focal point to organize the implementation of evaluating the compliance with Good Clinical Practice of business facilities conducting clinical drug trials and non-commercial facilities accepting clinical drug trials;

b) Taking the lead and coordinating with related units to disseminate and guide the contents of this Circular;

c) Serving as the focal point and coordinating with relevant units to guide the implementation of this Circular to Provincial Health Departments, Sectoral Health Services, and clinical drug trial facilities within their assigned functions and tasks;

d) Compiling and publishing on the Science, Technology and Training Department's website the list of business facilities conducting clinical drug trials and non-commercial facilities accepting clinical drug trials nationwide that have obtained certificates of qualification for pharmaceutical business and GCP certification, updating the status of certificates of qualification for pharmaceutical business and GCP certification, GCP compliance status, and other information as prescribed in Clause 4, Article 11 of this Circular, within their assigned functions and tasks;

đ) Publishing updated GCP documents on the Ministry of Health's electronic portal and the Science, Technology and Training Department's website;

e) Serving as the focal point or coordinating with the Ministry of Health Inspectorate and related units under the Ministry of Health to inspect and handle violations according to their authority;

g) Receiving and reviewing dossiers for clinical drug trials, guiding organizations, individuals with drugs for trial, and facilities accepting clinical drug trials to comply with the provisions of this Circular and other relevant laws;

h) Serving as the focal point to assist the Ministry of Health in organizing meetings of the National Ethics Council to review research protocols for clinical drug trials, changes to research protocols for clinical drug trials, and acceptance of clinical drug trial research; implementing the approval of the results of clinical drug trials;

i) Organizing regular or spot inspections of the research process.

2. The Drug Administration Department, Ministry of Health shall be responsible for:

a) Serving as the focal point to organize the implementation of evaluating the compliance with Good Clinical Practice of business facilities conducting bioequivalence testing of drugs and non-commercial facilities accepting bioequivalence testing of drugs;

b) Coordinating with related units to disseminate the contents and guide the implementation of this Circular;

c) Compiling and publishing on the Drug Administration Department's website the list of business facilities conducting bioequivalence testing of drugs and non-commercial facilities accepting bioequivalence testing of drugs nationwide that have obtained certificates of qualification for pharmaceutical business and GCP certification, updating the status of certificates of qualification for pharmaceutical business and GCP certification, GCP compliance status, and other information as prescribed in Clause 4, Article 11 of this Circular, within their assigned functions and tasks;

d) Serve as the coordinating entity, working with relevant units under the Ministry of Health to inspect and audit compliance with GCP requirements of businesses providing biological equivalence testing services for drugs and non-commercial drug equivalence testing facilities, and handle violations within their authority.

3. Provincial Health Departments are responsible for:

a) Coordinate with related units to disseminate this Circular and provide guidance on its implementation to units within their jurisdiction;

b) Participate in inspection teams evaluating GCP compliance; supervise and handle violations within their authority regarding GCP adherence by clinical drug testing facilities under their management;

4. Clinical drug testing facilities shall be responsible for:

a) Implementing this Circular in accordance with the actual conditions of the facility;

b) Ensuring compliance with GCP principles and standards throughout the operation of the facility;

c) Conducting clinical drug testing activities within the scope permitted based on compliance with legal regulations;

d) Adhering to the provisions concerning deadlines, documentation, and procedures for assessing GCP compliance as stipulated in this Circular;

đ) Subject themselves to surprise inspections, audits, and evaluations by competent state agencies regarding the maintenance of GCP compliance in accordance with legal provisions;

Article 30. Responsibility for Implementation

The Director of the Science, Technology and Training Department, the Director of the Drug Administration Department, the Head of the Ministry's Office, the Inspector General of the Ministry, the Heads of Departments, Directors of Bureaus, and General Directors of the General Bureaus under the Ministry of Health, the Heads of subordinate units of the Ministry of Health, and related organizations and individuals are responsible for enforcing this Circular;

During implementation, if there are difficulties or obstacles, relevant agencies, organizations, and individuals should promptly report them to the Ministry of Health (Science, Technology and Training Department) for consideration and resolution./.