Circular No. 45/2024/TT-BYT amending Circular No. 11/2018/TT-BYT on the quality of drugs and raw materials for drug production issued by the Minister of Health on February 7, 2025.

CIRCULAR

AMENDMENTS AND SUPPLEMENTS TO CERTAIN ARTICLES AND ANNEXES OF CIRCULAR NO. 11/2018/TT-BYT DATED MAY 4, 2018 ISSUED BY THE MINISTER OF HEALTH ON THE QUALITY OF DRUGS AND RAW MATERIALS FOR DRUGS

Pursuant to the Law on Medicines dated April 6, 2016;

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

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

Pursuant to Decree No. 95/2022/NĐ-CP dated November 15, 2022 of the Government stipulating the functions, tasks, powers, and organizational structure of the Ministry of Health;

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

The Minister of Health issues this Circular to amend and supplement certain articles and annexes of Circular No. 11/2018/TT-BYT dated May 4, 2018 issued by the Minister of Health on the quality of drugs and raw materials for drugs.

Article 1. Amends and supplements certain articles and annexes of Circular No. 11/2018/TT-BYT dated May 4, 2018 issued by the Minister of Health on the quality of drugs and raw materials for drugs.

1. Amends Point c Clause 1 Article 4 as follows:

“c) In cases where a production facility announces the application of one of the pharmacopoeias specified in Point a of this Clause but uses a testing method different from the method recorded in the monograph of the drug or raw material for drug in the selected pharmacopoeia, it must prove the equivalence between the manufacturer's testing method and the method recorded in the pharmacopoeia. The test results using the method recorded in the pharmacopoeia serve as the basis for concluding the quality of the drug.

In cases where the formulation components or manufacturing process of the drug affect the accuracy and reliability of the test according to the regulations, the production facility must provide explanations and information in the drug registration dossier or user guide. The test results using the method recorded in the approved quality standard in the registration dossier serve as the basis for concluding the quality of the drug;”

2. Amends Clause 2 Article 6 as follows:

“2. For drugs and raw materials for drugs that have been granted circulation permits: Within a maximum period of two years from the date of issuance of the latest version of the pharmacopoeia, the registration entity and the production facility are responsible for updating the quality standards of drugs and raw materials for drugs according to the provisions of that version of the pharmacopoeia. If the corresponding monograph in the pharmacopoeia changes the quality criteria and quality levels in a stricter and higher quality direction, the drug registration entity must implement change procedures as stipulated in Chapters III and IV of Circular No. 08/2022/TT-BYT dated September 5, 2022 issued by the Minister of Health on the registration for circulation of drugs and raw materials for drugs.”

3. Amends Point a Clause 2 Article 10 as follows:

“a) Review the dossier, conduct testing of vaccine and medical product samples received.

In cases where it is necessary to ensure the supply of vaccines and medical products to meet urgent needs for national defense, security, epidemic prevention, and disaster relief, the National Institute of Vaccine and Medical Product Quality Control shall review the Manufacturer’s Batch Test Report, storage conditions, transportation conditions, and check some quality indicators to proceed with releasing the batch;”

4. Amends Point d Clause 2 Article 11 as follows:

“d) Certificate of quality from the competent authority of the exporting country and the Manufacturer’s Batch Test Report accompanying each imported batch of vaccines and medical products (a certified copy stamped by the importer);”

5. Amends Clause 3 Article 11 as follows:

“3. The production facility and the importer are responsible for the legality of the documents provided by them.

In cases where it is necessary to ensure the supply of vaccines and medical products to meet urgent needs for national defense, security, epidemic prevention, and disaster relief, the importer may be exempted from submitting the production batch dossier as stipulated in Point c Clause 2 of this Article and the Certificate of Quality from the competent authority of the exporting country as stipulated in Point d Clause 2 of this Article (the Manufacturer’s Batch Test Report and the Data Sheet tracking storage conditions during transportation are mandatory).”

6. Amends Point a Clause 2 Article 12 as follows:

“a) Within 24 hours from the time of receiving information about drugs violating the provisions at Points a, c, d, and đ Clause 1 of this Article, the Ministry of Health (Drug Administration Department) will determine the level of violation of the drug and conclude on the recall of the non-compliant drug based on an assessment of the risk to the health of users.

In cases where consultation with the Advisory Council for Drug Registration is required to determine the level of violation as stipulated in Section IV of Annex II attached to this Circular, the deadline for determining the level of violation of the drug must be completed within a maximum of seven days;”

7. Amends Clause 1 Article 15 as follows:

“1. Drugs subject to recall may be rectified and re-exported in the following cases:

a) Drugs violating Level 3 and not falling under the circumstances stipulated in Point b Clause 2 of this Article;

b) Multi-component drugs packaged together in outer packaging, with individual components packaged in different direct packaging, where one or more components do not meet quality standards. Based on the level of violation of the component drug, such component may be rectified, re-exported, or destroyed according to regulations. Other components meeting quality standards may be repackaged accordingly.”

8. Adds Article 15a after Article 15 as follows:

"Article 15a. Suspension of sale, use, and sealing for storage of drugs showing signs of being unsafe for users.

1. Receiving information about drugs showing signs of being unsafe for users:"

The Ministry of Health (Drug Administration Department) receives information accompanied by relevant file materials (if any) regarding drugs that show signs of being unsafe for users from:

a) Competent authorities (including police, customs, market management, inspection, Vietnamese diplomatic missions abroad, foreign diplomatic missions in Vietnam);

b) World Health Organization, drug regulatory agencies or foreign health regulatory agencies;

c) Provincial Departments of Health;

d) Drug Information Center and Adverse Drug Reaction Monitoring Center;

đ) Drug manufacturing, trading, using organizations and other competent authorities, organizations, individuals.

2. Forms of information on drugs showing signs of being unsafe for users:

a) Official documents from the authorities specified in point a, c, and d of Clause 1 of this Article sent directly or through official mail to the Ministry of Health or via the electronic document management system of the Ministry of Health;

b) In addition to the forms prescribed in point a of this clause, official documents from the authorities specified in point b of Clause 1 of this Article may be sent via email or posted on the official website of the authority;

c) Complaints, reports or direct presentations at competent authorities according to the laws on complaints and denunciations by the authorities, organizations, individuals specified in point đ of Clause 1 of this Article.

3. Drugs showing signs of being unsafe for users include:

a) Drugs with serious or repeated adverse reaction reports related to the drug but not previously known adverse reactions of the drug;

b) Suspected drugs containing harmful substances or impurities exceeding safe limits for users;

c) Suspected substandard quality drugs;

d) Suspected counterfeit or non-genuine source drugs;

đ) Drugs produced from raw materials of unknown origin or not meeting quality standards;

e) Suspected drugs produced at facilities seriously violating Good Manufacturing Practices for drugs and active pharmaceutical ingredients or not confirmed by the drug regulatory agency to maintain production conditions.

4. Responsibilities of the Ministry of Health (Drug Administration Department) in handling information, temporarily suspending trade, use, and sealing storage of drugs showing signs of being unsafe for users:

a) Within no more than seven working days from the date of receiving information as stipulated in Clause 1 and Clause 2 of this Article, the Ministry of Health (Drug Administration Department) reviews received information, collaborates with at least one of the specialized agencies (Advisory Council for Drug Registration, Advisory Council for Vaccine Usage, Central Institute for Drug Control, Ho Chi Minh City Institute for Drug Control, National Institute for Vaccine and Biomedical Control, Specialized Hospital Pharmaceutical and Treatment Advisory Council) or inspection, police, customs, market management agencies if necessary, to assess the risk of impact on user health, determine the scope of temporarily suspending trade, use of drugs showing signs of being unsafe for users as specified in Clause 3 of this Article;

b) Within no more than three days from the date of concluding that the drug poses a risk to user health, the Ministry of Health (Drug Administration Department) issues a notice temporarily suspending production, import, distribution, use, and sealing of one or several batches or types of drugs showing signs of not ensuring safety for users;

c) The temporary suspension period for trade, use, and sealed storage of drugs showing signs of not ensuring safety for users to conduct verification shall be as follows:

The temporary suspension period shall not exceed two months from the date of issuance of the document. In complex cases or due to insufficient domestic technical conditions for drug analysis and testing, the suspension period may be extended by no more than two additional months.

If the above time limit is exceeded, in cases where the police, market management, customs, inspection authorities issue documents requesting continued temporary suspension of trade and use to serve the investigation and verification process, the suspension period will be extended based on current regulations and the requirements of these functional authorities;

d) The Ministry of Health (Drug Administration Department) has the responsibility to coordinate with relevant functional agencies, organizations, and individuals to conduct verification and draw conclusions on drug quality and the safety level for users.

For cases of information on drugs specified in points a and b of Clause 3 of this Article, the Ministry of Health (Drug Administration Department) reports to the Advisory Council for Drug Registration or the Advisory Council for Vaccine Usage (for vaccines) for consideration and conclusion. If sufficient grounds are needed for the conclusion, central-level drug testing institutions (Central Institute for Drug Control, Ho Chi Minh City Institute for Drug Control, or National Institute for Vaccine and Biomedical Control) will conduct analysis/testing to determine drug quality.

For cases of information on drugs specified in points c and đ of Clause 3 of this Article, the Ministry of Health (Drug Administration Department) directs and coordinates with the Central Institute for Drug Control/Ho Chi Minh City Institute for Drug Control, National Institute for Vaccine and Biomedical Control to conduct analysis/testing and conclude on the quality of drugs and raw materials.

For cases of information on suspected counterfeit drugs, drugs, and raw materials of unknown or non-genuine sources specified in points d and đ of Clause 3 of this Article, the Ministry of Health (Drug Administration Department) issues a document transferring information to the competent authority (Police/Market Management/Customs/Inspection Department) along with relevant files and materials for investigation and verification according to their functions and legal provisions.

In the case of drug information specified in Point e Clause 3 of this Article, the Ministry of Health (the Drug Administration Department, the Inspectorate) shall conduct unannounced inspections and audits of production facilities to ensure compliance with production conditions for domestic pharmaceutical production and business establishments, or cooperate with competent authorities to handle production facilities located abroad.

d) Within three days from the conclusion that the drug does not violate regulations or exceeds the notification period for temporarily suspending sales as stipulated in Point c of this Clause without concluding that the drug violates regulations, the Ministry of Health (the Drug Administration Department) shall issue a document to allow the establishment to continue producing, importing, distributing, and using the drug or batches of drugs that meet quality standards and are still within their shelf life.

In the case where the conclusion is that the drug violates regulations and does not ensure safety for users, the Ministry of Health (the Drug Administration Department) shall issue a document to recall drugs that have been temporarily suspended from distribution and use, and stop production and importation of drugs that do not ensure safety for users; impose administrative penalties or transfer the case to competent authorities for criminal responsibility according to regulations.

5. Responsibilities of the Provincial Health Departments in handling information, temporarily suspending business and use, and sealing and storing drugs that show signs of being unsafe for users:

a) The Provincial Health Departments shall be responsible for disseminating the conclusions of the Ministry of Health to drug business and usage establishments within their jurisdiction and supervise the temporary suspension of business and use, and sealing and storing of drugs that show signs of being unsafe for users.

b) Disseminate the Ministry of Health's notification allowing establishments to continue business and use of drugs or to recall drugs; supervise establishments to comply with the recall process as prescribed.

c) Cooperate with competent authorities within their jurisdiction to conduct inspections, checks, and verify information related to drugs that show signs of not ensuring safety as mentioned above occurring within their jurisdiction or as requested by the Ministry of Health; report results to the Ministry of Health (the Drug Administration Department, the Inspectorate).

6. Responsibilities of pharmaceutical business establishments and drug usage establishments:

a) Report fully and promptly to the Ministry of Health (the Drug Administration Department) or the Provincial Health Departments about cases of drugs showing signs of not ensuring safety for users.

b) Implement the temporary suspension of business and use, and sealing and storing of drugs that show signs of being unsafe for users according to the Ministry of Health's (the Drug Administration Department) notification; self-seal and store drugs according to the storage conditions indicated on the label.

Cooperate with competent authorities during the verification process of drugs that show signs of being unsafe for users (providing relevant files, documents, and evidence to support the verification process).

c) Continue business and use of drugs according to the Ministry of Health's (the Drug Administration Department) notification.

Implement the recall of drugs that do not ensure safety for users according to the Ministry of Health's (the Drug Administration Department) recall document when such drugs must be recalled according to regulations."

9. Amend Clause 3 of Article 16 as follows:

"3. Responsibilities of the Provincial Health Departments:

a) Organize notifications and dissemination to pharmaceutical production and business establishments, medical examination and treatment establishments within their jurisdiction regarding documents temporarily suspending distribution and use, recalling drugs, and post them on the Provincial Health Department’s website.

b) Conduct or instruct testing centers to take additional samples of suspected substandard drugs according to Point b Clause 1 or Point b Clause 2 of Article 14 of this Circular.

c) Supervise the recall of drugs within their jurisdiction; handle and penalize establishments violating drug quality or recall regulations according to their authority; report handling and penalty results to the Drug Administration Department, the Inspectorate.

d) Participate or implement evaluations of the effectiveness of drug recalls by pharmaceutical business establishments within their jurisdiction according to the Ministry of Health's (the Drug Administration Department) directives. Report to the Ministry of Health (the Drug Administration Department) about cases where production establishments, import establishments, and wholesale establishments fail to properly execute drug recalls.

e) Organize or participate in forced drug recalls."

10. Amend Point c Clause 4 of Article 18 as follows:

"c) Establish a system of files and documents to ensure tracking of drug circulation processes. Monitor and supervise the quality of drugs and raw materials for drugs sold by businesses; promptly identify and handle substandard drugs, report to management and quality control agencies. Comply with sample collection for inspection by quality management agencies, issue invoices for payment of inspected samples according to regulations."

11. Amend Clause 2 Section II Appendix II as follows:

"2. Drugs produced from raw materials that do not meet quality standards, except in cases where non-compliant raw materials are allowed to be rectified or recycled according to Clause 3 Article 104 of Decree No. 54/2017/NĐ-CP dated May 8, 2017 of the Government detailing certain provisions and implementation measures of the Medicine Law;"

12. Amend Clause 3 Section II Appendix II as follows:

"3. Drugs lacking evidence of quality control during production and before release (except in cases stipulated in Clause 5 Section I);"

13. Amend Clause 10 Section II Appendix II as follows:

"10. Drugs failing quality standards for microbial contamination (except in cases stipulated in Clauses 10 and 11 Section I);"

14. Amend Clause 20 Section II Appendix II as follows:

"20. Drugs failing quality standards for sedimentation in injectable suspensions;"

15. Add Clause 25 Section II Appendix II as follows:

"25. Drugs failing quality standards for uniformity of dosage units;"

16. Amend Clause 19 Section III Appendix II as follows:

"19. Drugs violating average weight specifications, drugs produced inconsistently with registered drug dossier: changes in tablet weight, excipient ratio, type of excipient, and remaining test results meeting quality standards: no recall; handle according to drug registration dossier violations."

17. Repeal Point e Clause 1 of Article 12.

Article 2. Effective Date

This Circular takes effect from February 7, 2025.

Article 3. Transitional Provisions

For drug registration files, raw material drug registration files; vaccine and medical product release certificate application files submitted before this Circular takes effect shall continue to be processed according to the regulations in force at the time of submission, except where the registering entity, manufacturing entity, or importing entity voluntarily chooses to implement the new regulations from the date this Circular takes effect.

Article 4. Reference Provisions

In cases where the referenced documents in this Circular are replaced or amended, implementation shall be carried out in accordance with the replaced document or the amended document.

Article 5. Responsibilities for Implementation

The Director of the Drug Administration Department, the Head of the Ministry's Office, the Head of the Ministry's Inspectorate, the Heads of units under and affiliated to the Ministry of Health, provincial and municipal health departments, pharmaceutical business entities, and other relevant agencies, organizations, and individuals are responsible for implementing this Circular.

Any issues encountered during implementation should be reported to the Ministry of Health (Drug Administration Department) for consideration and resolution.