Circular No. 11/2018/TT-BYT on the quality of drugs and raw materials for drug production

CIRCULAR

Provisions on drug quality, raw materials for drugs

 

 

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

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

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

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

The Ministry of Health issues this Circular on drug quality, raw materials for drugs.

 

PART I

GENERAL PROVISIONS

Article 1. Scope of Regulation

This Circular stipulates the application of drug quality standards (chemical drugs, herbal drugs, vaccines, biological products), raw materials for drugs (except herbal drugs); testing procedures for drugs and raw materials for drugs, and recall and handling procedures for non-compliant drugs.

Article 2. Interpretation of Terms

In this Circular, certain terms are understood as follows:

1. Drug quality standards, raw material quality standards are documents specifying technical characteristics, including quality criteria, quality levels, testing methods, and other management requirements related to drug and raw material quality.

2. ofL"5. The pre-tax weighted average cost of capital i (%) is determined according to the formula below: is the abbreviation for the English term "Good Laboratory Practices", translated into Vietnamese as "Good Laboratory Practice for Drugs".

3. WHO is the abbreviation for the English term "World Health Organization", translated into Vietnamese as World Health Organization.

4. ICH is the abbreviation for the English term "International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use", translated into Vietnamese as International Conference on Harmonization of Technical Requirements for Pharmaceutical Registration for Human Use.

Chapter II

APPLICATION OF DRUG QUALITY STANDARDS,

RAW MATERIALS FOR DRUGS

Article 3. General Provisions

1. Drug business establishments, compounding facilities shall apply drug and raw material quality standards according to the pharmacopoeia or enterprise standards for drugs and raw materials produced or compounded by the establishment.

2. Drug business establishments, compounding facilities must conduct validation and evaluation of the testing methods recorded in the drug and raw material quality standards published by the production facility. Validation of testing methods shall be carried out in accordance with the guidelines on analytical procedure validation of the Association of Southeast Asian Nations or ICH as specified in the Circular on drug registration and raw material registration issued by the Minister of Health.

3. The Ministry of Health shall organize the review of files and approve drug and raw material quality standards in accordance with regulations on drug registration and raw material registration, and regulations on import permit issuance for unregistered drugs and raw materials.

Article 4. Application of Pharmacopoeia1. Application of Vietnamese Pharmacopoeia, reference pharmacopoeias:

a) Drug business establishments, compounding facilities may apply the Vietnamese Pharmacopoeia or one of the following reference pharmacopoeias: European Pharmacopoeia, British Pharmacopoeia, United States Pharmacopeia, International Pharmacopoeia, Japanese Pharmacopoeia;

b) The application of standards in these pharmacopoeias as specified in point a of this Clause must include all provisions on quality criteria, quality levels, and testing methods specified in the monographs of the corresponding drugs and raw materials in the applied pharmacopoeia; including the general quality criteria, quality levels, and testing methods specified in the appendices of the pharmacopoeia;

c) In cases where a manufacturing facility publishes the application of one of the pharmacopoeias as specified in point a of this Clause but uses a different testing method from that recorded in the individual monograph of the drug or raw material in the selected pharmacopoeia, it must prove the equivalence between the manufacturer's testing method and the testing method recorded in the pharmacopoeia. Test results using the testing method recorded in the pharmacopoeia serve as the basis for concluding the drug quality;

d) For herbal drugs, drug business establishments, compounding facilities may apply the pharmacopoeia as specified in point a of this Clause or the pharmacopoeia of the country of origin of the drug.

2. Application of foreign pharmacopoeias other than those specified in point a of Article 1:

If a drug business establishment or compounding facility applies a foreign pharmacopoeia other than the reference pharmacopoeias specified in point a of Article 1, the applied quality standard must at least meet the following requirements:

a) Meet the requirements for quality criteria and quality levels specified in the corresponding quality standard monographs of the Vietnamese Pharmacopoeia or one of the reference pharmacopoeias;

b) The applied general testing methods must be consistent with the corresponding general testing methods recorded in the Vietnamese Pharmacopoeia or one of the reference pharmacopoeias specified in point a of Article 1.

b) The general testing method applied must be consistent with the corresponding general testing method recorded in the Vietnamese Pharmacopoeia or one of the reference pharmacopoeias specified in point a, Clause 1 of this Article.

Article 5. Application of basic standards

1. Basic standards for drugs and drug raw materials must comply with the provisions set out in point b, Clause 2, Article 102 of the Drug Law, specifically as follows:

a) Meeting the requirements of quality indicators, quality levels specified in the corresponding monographs of the Vietnamese Pharmacopoeia and quality indicators, quality levels, and common testing methods prescribed in the Appendices of the Vietnamese Pharmacopoeia;

b) In cases where the Vietnamese Pharmacopoeia or the referenced pharmacopoeia mentioned in point a, Clause 1, Article 4 of this Circular does not have corresponding monographs on drugs or drug raw materials, the standard shall be established based on scientific research results (including product development results) or according to the regulations of another foreign pharmacopoeia.

2. The basic standards for compounded and prepared drugs at medical examination and treatment facilities shall be established, evaluated for suitability, and issued by the head of the facility.

Article 6. Updating quality standards and applying updated pharmacopoeias

1. For registered drugs and drug raw materials: At the time of submitting registration files, the quality standards of drugs and drug raw materials must meet the pharmacopoeia in one of the following two situations:

a) The current version of the pharmacopoeia;

b) Previous versions of the pharmacopoeia up to two years prior to the effective date of the current version.

2. For drugs and drug raw materials that have been granted permission for circulation: Within a maximum period of two years from the date the latest version of the pharmacopoeia was issued, the registering entity and the manufacturing entity are responsible for updating the quality standards of drugs and drug raw materials according to the provisions of that version of the pharmacopoeia.

3. During the circulation of drugs and drug raw materials, if the manufacturing entity or the registering entity discovers factors seriously affecting the quality, safety, and efficacy of the drugs, or upon request of the Ministry of Health (Drug Administration Department), the manufacturing entity must update the quality standards of drugs and drug raw materials to control such influencing factors.

PART III

TESTING OF DRUGS AND DRUG RAW MATERIALS

Article 7Testing of drugs and drug raw materials

1. Testing must be conducted in accordance with the approved and updated quality standards of drugs and drug raw materials.

If the quality standards of drugs and drug raw materials have not been updated, the testing entity shall apply the corresponding pharmacopoeia as stipulated in Clause 1 and Clause 2 of Article 6 of this Circular, calculated from the production date of the batch of drugs and drug raw materials being tested.

For compounded and prepared drugs at medical examination and treatment facilities, testing shall be carried out according to the quality standards established and issued by the facility.

2. Sampling of drugs and drug raw materials for testing shall be conducted in accordance with the provisions of Appendix I, and the sampling record shall be made in accordance with Form No. 01 of Appendix III attached to this Circular.

3. Reporting test and analysis results of drugs and drug raw materials:

a) Test and analysis results of drug samples and drug raw material samples shall be reflected on the test report or analysis report as specified in Form No. 02 and Form No. 03 of Appendix III attached to this Circular;

b) Within a maximum period of 15 days from the date of receiving the drug sample, the testing entity must respond with the test and analysis results of the drug sample taken by the quality control agency in the following cases:

- Drugs with information about serious adverse reactions;

- Drugs from entities that have serious violations regarding compliance with Good Manufacturing Practices;

- Drugs sampled for supplementary testing as provided for in point b, Clause 1 and point b, Clause 2 of Article 14 of this Circular.

c) Within a maximum period of 20 days from the date of receiving the drug sample, the testing entity must respond with the test and analysis results in the following case:

- Drugs that must be tested before circulation as stipulated in Clause 1 of Article 8 of this Circular;

- Drugs not falling under the cases specified in points b and d of this clause.

d) Within a maximum period of 30 days from the date of receiving the drug sample or drug raw material sample, the testing entity must respond with the test and analysis results in the following cases:

- Drugs and drug raw materials with tests requiring extended testing times;

- Drugs and drug raw materials with quality standards requiring re-evaluation or reassessment of test results;

- Drugs and drug raw materials suspected of having incorrect components or quality, requiring application of different testing methods than those recorded in the registered quality standards;

- Drugs and drug raw materials with tests that the testing entity lacks the necessary conditions to conduct (e.g., lack of equipment, chemicals, reagents, reference substances).

e) In cases where the response deadlines for test and analysis results as stipulated in points b, c, and d of this clause cannot be met, the testing entity must provide explanations in the accompanying test report or analysis report;

f) Within 24 hours from the issuance of the test report or analysis report, the testing entity must send the test report or analysis report to the quality control agency, the manufacturing entity, the importing entity, and the entity from which the sample was taken.

In cases where drug samples or drug raw material samples do not meet quality standards, within 24 hours from the issuance of the analysis report or test report, the testing entity must send a notification letter regarding non-compliant drug samples or drug raw material samples along with the test report or analysis report to the Ministry of Health (Drug Administration Department) via administrative documents and electronic documents (scanned copies) to the email address: [email protected] or text message to the Drug Administration Department's phone number from the official contact address and phone number of the testing entity and the Health Department where the drug samples or drug raw material samples were taken.

g) For drug samples and raw materials for drugs sent by pharmaceutical business establishments, users, organizations, or individuals for analysis, testing, or quality standard evaluation, the time to provide the analytical and testing results shall be agreed upon by the parties.

4. Complaints and Resolution of Testing Result Disputes:

a) In case of disagreement with the testing results of the sample, within five days from the date of receiving the notification of the testing results of the drug sample or raw material sample, the pharmaceutical business establishment has the right to request the state quality control agency to designate another testing facility to conduct analysis and testing to determine the drug quality testing results.

b) The retesting of disputed quality criteria shall be carried out at the testing facility designated by the Ministry of Health pursuant to Clause 2, Article 105 of the Drug Law.

5. Sample Storage:

a) After being tested and having their quality determined, drugs and raw materials for drugs must be retained as samples. Retained drug and raw material samples must be sealed and stored according to the conditions stated on the label.

b) Sample storage period:

- For production facilities and importers of drugs and raw materials for drugs: finished drug product samples must be retained for at least twelve months after the expiration date of the drug; active ingredient raw material samples used for drug production must be retained for at least twelve months after the expiration date of the finished product produced from such raw materials;

- For drug testing facilities: the retention period for samples must be at least twelve months after the expiration date of the drug; or twenty-four months from the date of sampling for drug samples taken for quality testing purposes, or from the date of receipt for samples submitted in cases of supplementary sampling as stipulated in point b, Clause 1 and point b, Clause 2 of Article 14 of this Circular.

6. Record Keeping of Documents and Materials:

a) Documents related to drug quality inspection work and raw materials for drugs must be kept in accordance with the Law on Archives and relevant guiding documents.

b) Documents related to drugs and raw materials for drugs containing addictive substances, psychotropic substances, precursor substances used for drugs, and radioactive drugs: the storage period must be at least two years from the expiration date of the drug.

c) Documents that have exceeded the retention period shall be processed in accordance with current regulations.

Article 8. Pre-release testing for drugs is provided for in Clause 4, Article 103 of the Drug Law.

1. Drugs falling under any of the following circumstances must be tested by a testing facility designated by the Ministry of Health (Drug Administration Department) before circulation:

a) Drugs specified in points a and b of Clause 4, Article 103 of the Drug Law;

b) Blood-derived biological products and plasma-derived biological products;

c) Imported drugs regulated in Article 70 of Decree No. 54/2017/ND-CP dated May 8, 2017, of the Government detailing certain provisions and implementing measures of the Drug Law (hereinafter referred to as Decree No. 54/2017/ND-CP);

d) Drugs produced by foreign manufacturing facilities listed in the list of manufacturing facilities with substandard drugs published by the Ministry of Health (Drug Administration Department).

2. Provisions regarding the determination of drug quality through testing:

a) Sampling of drugs:

- For drugs specified in points a, b, and c of Clause 1 of this Article, sampling shall be conducted by the manufacturing facility (for domestically produced drugs) or the importer (for imported drugs);

- For drugs specified in point d of Clause 1 of this Article, the importer shall request the quality control agency or the state testing facility to take samples.

b) The importer shall send the collected drug sample along with a photocopied original test certificate from the manufacturer to the designated drug testing facility in accordance with Clause 3 of this Article for testing to determine the drug quality according to the approved quality standards.

c) Manufacturing facilities and importers of vaccines and blood-derived biological products and plasma-derived biological products containing antibodies, as specified in points a and b of Clause 1 of this Article, shall submit samples in accordance with Articles 10 and 11 of this Circular.

d) Within the time limit specified in point c, Clause 3, Article 7 of this Circular, the testing facility must provide the testing results for the received drug samples.

3. The Ministry of Health (Drug Administration Department) designates a testing facility that has been issued a Certificate of Compliance for pharmaceutical business operations with the scope of drug testing or a testing facility specified in Clause 1, Article 35 of the Drug Law, which meets GLP requirements, to perform the drug testing as specified in Clause 1 of this Article.

If the testing facility lacks the conditions to conduct one or more tests, the testing facility must notify and cooperate with the manufacturing facility or importer to send samples for these tests at another testing facility meeting GLP requirements or a laboratory meeting ISO/IEC 17025 standards and having the necessary conditions to perform the tests.

4. Monthly, the designated testing facility must report the drug testing results to the Ministry of Health (Drug Administration Department) in accordance with Form No. 07 of Appendix III attached to this Circular.

5. The Ministry of Health (Drug Administration Department) publishes and updates the list of designated testing facilities in accordance with Clause 3 of this Article on the Drug Administration Department's website.

6. Manufacturing facilities and importers of drugs are responsible for:

a) Paying the testing fees for determining the quality of drugs produced or imported in accordance with the regulations;

b) Providing reference standards, comparison standards, and impurity standards to the testing facility when the Central Institute for Drug Control, Ho Chi Minh City Institute of Drug Control, National Institute for Vaccine and Biomedical Research, or other testing facilities have not established them;

c) Only releasing and distributing batches of drugs that have passed the quality testing standards.

7. Testing of vaccines, blood-derived biological products, and plasma-derived biological products containing antibodies is carried out in accordance with Articles 10 and 11 of this Circular.

Article 9. The testing period for drugs from facilities listed in the list of manufacturing facilities with substandard drugs and the process of removing them from this list

1. The testing period shall commence from the date of importation of the first batch of drugs after the Ministry of Health (the Drug Administration Department) publishes the List of Manufacturing Facilities with Quality Violating Drugs as follows:

a) Six months for a manufacturing facility with one batch of drugs violating level 3;

b) Twelve months for a manufacturing facility with one batch of drugs violating level 2 or two or more batches of drugs violating level 3;

c) Twenty-four months for a manufacturing facility with one batch of drugs violating level 1 or two or more batches of drugs violating level 2;

d) In cases where a manufacturing facility continues to have quality-violating drugs, the testing period will be extended cumulatively.

2. A manufacturing facility may be removed from the List of Manufacturing Facilities with Quality Violating Drugs when it fulfills all the following requirements:

a) The importing entity conducts full drug testing before releasing them into circulation in accordance with the time limit specified in Clause 1 of this Article;

b) The manufacturing facility or the drug registration entity submits a report in accordance with Form No. 07 of Appendix III issued together with this Circular, along with evidence of conducting comprehensive testing on all imported batches of drugs into Vietnam within the time limit specified in Clause 1 of this Article;

c) The manufacturing facility does not have any quality-violating drugs (including voluntary recalls due to quality issues) during the time limit specified in Clause 1 of this Article.

3. On a monthly basis, based on the reports from participating testing entities, as well as the reports from manufacturing facilities and drug registration entities, the Ministry of Health (the Drug Administration Department) will update and publish the List of Manufacturing Facilities with Quality Violating Drugs, removing the names of facilities that meet the requirements set out in Clause 2 of this Article from the said list.

Article 10Testing of vaccines, sera containing antibodies, and human blood and plasma derivatives

1. Manufacturing facilities and importers must submit samples and production records of vaccines, sera containing antibodies, and human blood and plasma derivatives to the National Institute of Vaccines and Biologicals for pre-release testing and evaluation. The sample submission form is stipulated in Article 11 of this Circular.

Manufacturing facilities and importers are only permitted to release and use batches of vaccines, sera containing antibodies, and human blood and plasma derivatives into circulation after receiving a quality certification from the National Institute of Vaccines and Biologicals confirming that the batch meets quality standards and is safe and effective.

2. Within the time limit specified in Clause 3 of Article 7 of this Circular, starting from the date of receipt of samples and records in accordance with Article 11 of this Circular, the National Institute of Vaccines and Biologicals shall proceed as follows:

a) Review the records and conduct testing on the submitted vaccine and biological product samples;

b) Issue a quality certification in accordance with Form No. 08 of Appendix III issued together with this Circular, specifying whether each requirement is met or not, and concluding on the quality, safety, and efficacy of the batch of vaccines and biological products;

c) Report the testing results to the Ministry of Health (the Drug Administration Department).

Article 11Records and samples for evaluating the quality, safety, and efficacy of vaccines, sera containing antibodies, and human blood and plasma derivatives

1. For domestically produced vaccines, sera containing antibodies, and human blood and plasma derivatives: The manufacturing facility must submit production records and samples of the batch of finished or semi-finished products to the National Institute of Vaccines and Biologicals, including:

a) Sample submission form;

b) Samples of vaccines and biological products for testing (quantity of samples for each type of vaccine and biological product as specified in the Guidelines on Pre-release Testing of Sera Containing Antibodies, Human Blood and Plasma Derivatives);

c) Summary production and quality control records of the batch of vaccines and biological products (a copy stamped and confirmed by the manufacturing facility);

d) Batch test report issued by the manufacturing facility.

2. For imported vaccines, sera containing antibodies, and human blood and plasma derivatives: Importers must submit production records and samples of the batch of products to the National Institute of Vaccines and Biologicals, including:

a) Sample submission form;

b) Samples of vaccines and biological products for testing (quantity of samples for each type of vaccine and biological product as specified in the Guidelines on Pre-release Testing of Sera Containing Antibodies, Human Blood and Plasma Derivatives);

c) Summary production and quality control records of the imported batch of vaccines and biological products (a copy stamped and confirmed by the manufacturing facility or the importer);

d) Quality certificates issued by the competent authority of the exporting country for each imported batch of vaccines and biological products (a copy stamped and confirmed by the importer);

đ) Temperature monitoring data log (cold chain) during the transportation of the imported batch (stamped and confirmed by the importer) from temperature recording devices, and freeze indicator results (if available).

3. Manufacturing facilities and importers are responsible for the legal validity of the documents provided by their entities.

Chapter IV

REGULATIONS ON DRUG RECALLS AND HANDLING OF VIOLATING DRUGS

Article 12Procedures for Compulsory Drug Recall

1. Receiving information on violating drugs:

The Ministry of Health (the Drug Administration Department) receives information on violating drugs from:

a) Evaluations by the Drug Registration Advisory Council or the Post-Vaccination Adverse Event Handling Advisory Council indicating that the drug does not ensure therapeutic effectiveness or safety;

b) Information on substandard drug quality from drug testing facilities;

c) Information on violating drugs discovered by the Drug Administration Department or health/drug inspection agencies;

d) Announcements of violating drugs from manufacturing facilities, management agencies, or national drug quality control agencies of foreign countries;

đ) Information on violating drugs discovered by police, customs, or market regulation authorities;

e) Information on drugs proposed for voluntary recall by pharmaceutical business entities.

2. Determining the Level of Violation:

a) Within twenty-four hours from the time of receiving information about drugs violating the provisions set forth in points a, c, d, đ, and e of Clause 1 of this Article, the Ministry of Health (Medicine Administration Department) shall conduct an assessment of the level of violation of the drugs and conclude on the recall of the non-compliant drugs based on a risk assessment for the health of users.

In cases where it is necessary to seek the opinion of the Advisory Council for Drug Registration to determine the level of violation as prescribed in Section IV of Appendix II attached hereto, the deadline for determining the level of violation of the drugs must be completed within a maximum of seven days.

b) The level of violation of the drugs is defined in Appendix II attached hereto;

c) For information about drugs violating the provisions set forth in point b of Clause 1 of this Article, the handling shall be carried out according to the provisions of Article 14 of this Circular.

3. Issuing the decision to recall drugs:

a) Within a period not exceeding twenty-four hours from the time of concluding on the recall of the drugs, the Ministry of Health (Medicine Administration Department) shall issue the decision to recall the drugs in accordance with the provisions of Clause 1 of Article 65 of the Medicine Law;

b) The recall decision must include the following information: drug name, registration number or import permit number, active ingredient name, concentration, dosage, formulation, batch number, expiration date, manufacturing facility, importing facility, level of recall, entity responsible for recalling the drug.

4. Announcing the decision to recall drugs:

a) The decision to recall drugs of the Ministry of Health (Medicine Administration Department) shall be announced through various means such as mail, fax, email, telephone, or mass media. The scope of announcing the recall decision is regulated in Clause 3 of Article 63 of the Medicine Law;

b) Immediately upon issuance of the recall decision, the Ministry of Health (Medicine Administration Department) shall publish the decision to recall drugs on the Ministry of Health's electronic portal, the Medicine Administration Department's website, and the national pharmaceutical database of the Ministry of Health;

The Health Department shall announce information about the recall decision on its website immediately after receiving the recall decision.

Domestic drug manufacturing facilities and importing entities must notify information about recalled drugs to drug trading and using entities that have purchased the drugs.

c) In cases of recalling drugs at Level 1, in addition to implementing the provisions stipulated in point b of this Clause, the recall decision must also be announced by the Ministry of Health on Vietnam Television and Voice of Vietnam Radio.

5. Implementing the recall of drugs:

a) Drug trading and using entities must cease supplying and using the drugs; store remaining drugs at their premises; compile a list of drug trading and using entities, individuals (if any) who have purchased the drugs, contact and accept returned drugs; return the drugs to the supplier;

b) Manufacturing facilities (for domestically produced drugs), importing entities (for imported drugs) must cooperate with entrusted importing entities or primary distribution entities to take responsibility for recalling the non-compliant drugs. The record of drug recall shall be conducted in accordance with Model No. 04 of Appendix III attached hereto.

In cases where drug trading and supplying entities fail to implement the recall of drugs or refuse to accept returned drugs, the entities or individuals purchasing and using the drugs shall report to the Health Department in their locality for handling in accordance with regulations.

c) The recall of drugs must be completed within the deadlines specified in Clause 3 of Article 63 of the Medicine Law.

6. Reporting Recall Results, Evaluating Recall Effectiveness, and Additional Handling:

a) Within one day for Level 1 recalls, three days for Level 2 and Level 3 recalls from the completion date of the recall, the entity responsible for the recall must submit a written report on the results of the recall to the Ministry of Health (Medicine Administration Department) and the Health Department in the locality where the drug trading entity responsible for the recall is located. The report shall include the following documents:

- A summary report on the recalled drugs in accordance with Model No. 05 of Appendix III attached hereto;

- A list of drug trading and using entities (including entities directly supplied from the entity responsible for the recall of non-compliant drugs and entities supplied from distribution entities) along with information on address, phone number, email (if available), quantity supplied, quantity of drugs recalled;

- Delivery and receipt records, return invoices, or other evidence demonstrating the recall of drugs;

- An evaluation report on the effectiveness of the drug recall;

- Investigation and assessment results of the causes, risk assessment of other batches of non-compliant drugs and/or other drugs produced on the same production line.

b) The Ministry of Health (Medicine Administration Department) shall review the report on the results of the recall as stipulated in point a of this Clause, evaluate or assign the Health Department to evaluate the effectiveness of the recall. If the effectiveness of the recall is assessed as insufficient, the product may still continue to circulate and be used, posing a risk of adverse effects on user health, the Medicine Administration Department shall coordinate with the Health Department and relevant authorities to enforce the recall.

Article 13. Procedure for Voluntary Recall of Medicines

1. Pharmaceutical business establishments that voluntarily recall medicines shall assess and determine the level of violation of the medicines themselves and report in writing to the Ministry of Health (Medicine Administration Department), specifying detailed information about the violating medicine, the level of violation, reasons for recall, and proposed measures to handle the recalled medicine as stipulated in Clause 3 and Clause 4, Article 15 of this Circular.

2. Within three days from the date of receipt of the report from the pharmaceutical business establishment, the Ministry of Health (Medicine Administration Department) shall review the report of the pharmaceutical business establishment, and determine the level of violation of the medicine according to the provisions in Appendix II issued together with this Circular.

a) In cases where it agrees with the proposal of the pharmaceutical business establishment regarding the third-level violation of the medicine, the Ministry of Health (Medicine Administration Department) shall issue a written agreement for the voluntary recall by the establishment.

b) In cases where it determines that the medicine violates at the first or second level, the Ministry of Health (Medicine Administration Department) shall implement the procedures for recalling medicines as stipulated in Clauses 3, 4, 5, and 6, Article 12 of this Circular.

c) In cases where additional or clarifying information is needed in the report of the pharmaceutical business establishment, the Ministry of Health (Medicine Administration Department) shall issue a written request for the establishment to provide supplementary information and explanations. Within five days from the date of receipt of the document from the Ministry of Health (Medicine Administration Department), the establishment must submit a supplementary written document and explanation.

3. Within twenty-four hours from the time the Ministry of Health (Medicine Administration Department) issues a written agreement for the voluntary recall by the establishment, the pharmaceutical business establishment shall issue a decision to recall the medicine, notify other business establishments and users, and carry out the recall procedures as stipulated in Clauses 5 and 6, Article 12 of this Circular.

Article 14. Handling of Substandard Medicines Based on Sampling Location

1. In cases where the sample of the violating medicine is taken by the quality control agency at retail pharmacies, grade III or IV medical examination and treatment facilities:

a) Within 24 hours from the time of receiving the test report or analysis sheet sent by the testing facility, the Department of Health shall seal the substandard drugs at the sampled outlet.

b) Within forty-eight hours from the time of receiving the test report or analysis sheet sent by the testing facility, the Ministry of Health (Medicine Administration Department) shall issue a written request for the registration establishment, production facility, or import establishment to take responsibility for:

- Reporting on the distribution of the medicine to the Ministry of Health (Medicine Administration Department);

- Requesting the quality control agency to take additional samples at domestic production facilities or import establishments for foreign medicines, and at least two wholesale facilities, including the wholesale facility that supplied the medicine to the sampled facility;

- Sending the collected samples to central-level testing facilities for quality control on non-conforming criteria.

c) In cases where at least one (one) of the additional samples does not meet quality standards, the Ministry of Health (Medicine Administration Department) shall determine the level of violation and conclude on the recall of the violating medicine according to the provisions in Appendix II issued together with this Circular, and issue a decision to recall the medicine as stipulated in Clause 3, Article 12 of this Circular. The scope and time limit for the recall shall be carried out according to the provisions in Clause 3, Article 63 of the Medicine Law.

d) In cases where all additional samples meet quality standards, the Ministry of Health (Medicine Administration Department) shall only determine the level of violation, conclude on the recall of the violating medicine, issue a decision to recall, and handle the medicine of the initially sampled facility.

2. In cases where the sample of the violating medicine is taken by the quality control agency at wholesale facilities, grade II or higher medical examination and treatment facilities:

a) Within 24 hours from the time of receiving the test report or analysis sheet sent by the testing facility, the Department of Health shall seal the substandard drugs at the sampled outlet.

b) Within forty-eight hours from the time of receiving the test report or analysis sheet sent by the testing facility, the Ministry of Health (Medicine Administration Department) shall issue a decision to recall the medicine in the province or centrally administered city where the sample was taken and at business establishments and users supplied by the wholesale facility that took the sample, as stipulated in Clause 3, Article 12 of this Circular, and issue a written request for the registration establishment, production facility, or import establishment to take responsibility for:

- Reporting on the distribution of the medicine to the Ministry of Health (Medicine Administration Department);

- Requesting the quality control agency to take additional samples of at least two medicines at another wholesale facility, including the wholesale facility that supplied the medicine to the sampled facility;

- Sending the collected samples to central-level testing facilities for quality control on non-conforming criteria.

c) In cases where at least one (one) of the additional samples does not meet quality standards, the Ministry of Health (Medicine Administration Department) shall determine the level of violation and conclude on the recall of the violating medicine according to the provisions in Appendix II issued together with this Circular, and issue a decision to recall the medicine as stipulated in Clause 3, Article 12 of this Circular. The scope and time limit for the recall shall be carried out according to the provisions in Clause 3, Article 63 of the Medicine Law.

d) In cases where all additional samples meet quality standards, the Ministry of Health (Medicine Administration Department) shall only implement the provisions in point b of this clause.

3. In cases where the sample of the violating medicine is taken by the quality control agency at production facilities, import establishments, or service storage facilities, or the medicine is determined to violate quality due to reasons during the production process, the Ministry of Health (Medicine Administration Department) shall determine the level of violation and conclude on the recall of the violating medicine according to the provisions in Appendix II issued together with this Circular, and issue a decision to recall the medicine as stipulated in Clause 3, Article 12 of this Circular. The scope and time limit for the recall shall be carried out according to the provisions in Clause 3, Article 63 of the Medicine Law.

Article 15. Handling of Recalled Medicines

1. Recalled medicines may be allowed to be rectified or re-exported in cases of third-level violations and not falling under the circumstances specified in point b, Clause 2 of this Article.

2. Recalled medicines must be destroyed if they fall under any of the following circumstances:

a) Recalled medicines due to first or second-level violations;

b) Recalled medicines due to third-level violations, which have been reviewed by the Ministry of Health (Medicine Administration Department) according to the provisions in Clause 3 and Clause 4 of this Article and concluded as not being able to be rectified or re-exported;

c) Recalled medicines due to third-level violations, which have been permitted by the Ministry of Health (Medicine Administration Department) to be rectified or re-exported but the establishment has failed to carry out such actions.

3. Procedures for Proposing Rectification of Recalled Medicines:

a) Establishments with recalled medicines shall submit a written document to the Ministry of Health (Medicine Administration Department) along with the rectification procedure, risk assessment for the quality and stability of the medicine, and a monitoring program for the quality, safety, and efficacy of the medicine during circulation.

b) Within a maximum of sixty days from the date of receipt of the rectification proposal from the establishment, the Ministry of Health (Medicine Administration Department) shall review and issue a written response agreeing or disagreeing with the rectification. If disagreement, the reasons must be clearly stated.

c) In cases where additional information needs to be supplemented or clarified regarding the remediation, within a maximum period of 60 days from the date of receipt of the document from the Ministry of Health (Drug Administration Department), the entity must submit supplementary documents and explanations. After this deadline, if the entity does not submit supplementary documents and explanations, the remediation request will lose its validity.

4. Procedures for requesting re-exportation of recalled drugs:

a) Entities with recalled drugs shall send a document to the Ministry of Health (Drug Administration Department) along with a re-export plan specifying the time and country of re-exportation;

b) Within a maximum period of 15 days from the date of receipt of the entity's request document, the Ministry of Health (Drug Administration Department) shall issue a written response agreeing or disagreeing with the re-exportation; in case of disagreement, the reasons must be clearly stated.

5. Remediation and re-exportation of recalled drugs can only be carried out after receiving a written agreement from the Ministry of Health (Drug Administration Department).

6. Drug destruction:

a) The head of the entity with drugs to be destroyed shall issue a decision to establish a drug destruction committee. The committee must consist of at least three members, including one representative responsible for professional matters;

b) The destruction of drugs must ensure safety for people and animals and prevent environmental pollution in accordance with laws on environmental protection;

c) Special controlled drug destruction must be carried out in accordance with Article 48 of Decree No. 54/2017/NĐ-CP;

d) The entity destroying the drugs must report to the Department of Health, accompanied by a record of drug destruction, in accordance with Model No. 06 of Appendix III issued together with this Circular.

7. The deadline for handling recalled drugs shall not exceed 12 months from the completion date of the recall process as stipulated in Points a, b, and c of Clause 3, Article 63 of the Medicine Law.

Article 16Responsibilities for recalling drugs

1. Responsibilities of pharmaceutical business entities, medical examination and treatment facilities, and users:

a) Implement the provisions of Clauses 1, 2, and 3 of Article 64 of the Medicine Law;

b) Regularly check and update information about drug recalls on the Ministry of Health’s electronic portal, the Drug Administration Department’s website, and the Department of Health’s website.

2. Responsibilities of the Drug Administration Department:

a) Receive information, determine the level of violation of drugs, and issue decisions to recall drugs;

b) Announce the decision to recall drugs in accordance with Point a of Clause 4, Article 12 of this Circular, publish information about recalled drugs on the Ministry of Health’s electronic portal and the Drug Administration Department’s website after issuing the recall decision. Coordinate with Vietnam Television and Voice of Vietnam to announce information about recalled drugs at Level 1 violations;

c) Examine reports and respond to proposals for voluntary recalls, proposals for remediation measures, and re-exportation of recalled drugs from pharmaceutical business entities;

d) Coordinate with relevant units (Ministry Inspectorate, Department of Health, Health Services) to inspect and supervise the organization and implementation of drug recalls; handle violative entities according to the law;

đ) Issue detailed guidelines on the procedures for processing and recalling drugs, evaluating the effectiveness of recall notifications from drug production and business entities;

3. Responsibilities of the Health Departments:

a) Publish information on the decision to recall drugs on the Department of Health’s website;

b) Organize announcements and dissemination of recall information to pharmaceutical production and business entities, medical examination and treatment facilities within their jurisdiction;

c) Conduct or instruct testing centers to cooperate with violative entities to take additional samples of drugs in accordance with Point b of Clause 1 or Point b of Clause 2 of Article 14 of this Circular;

d) Supervise drug recalls within their jurisdiction; handle and impose penalties on violative entities according to their authority;

đ) Participate or implement evaluations of the effectiveness of drug recalls from pharmaceutical business entities within their jurisdiction as directed by the Ministry of Health (Drug Administration Department). Report to the Ministry of Health (Drug Administration Department) on cases where production entities, import entities, and wholesale entities fail to fully implement drug recalls;

e) Organize or participate in forced drug recalls.

Chapter V

IMPLEMENTING PROVISIONS

Article 17. Effective Date

1. This Circular takes effect from June 20, 2018.

2. The following documents are abolished from the date this Circular takes effect:

a) Circular No. 09/2010/TT-BYT dated April 28, 2010, issued by the Minister of Health guiding the management of drug quality;

b) Circular No. 04/2010/TT-BYT dated February 12, 2010, issued by the Minister of Health guiding the sampling of drugs to determine quality.

Article 18. Implementation Organization

1. The Drug Administration Department shall be responsible for:

a) Taking the lead and coordinating with relevant units to organize publicity, dissemination, and implementation of this Circular;

b) Take the lead in coordinating with the Central Institute of Pharmaceutical Inspection, Ho Chi Minh City Institute of Pharmaceutical Inspection, National Institute of Vaccines and Biologicals to develop plans for sampling drugs for quality inspection, to be submitted to the Ministry of Health for review, approval, and budget allocation for implementation according to their authority.

Implement the sampling of drugs for quality inspection and update the Ministry of Health's drug quality inspection information database with details about the sampled drugs and raw materials (including information such as drug name, raw material name, concentration, dosage form, batch number, expiration date, registration certificate or import permit number, manufacturing entity, importing entity, sampling entity) and the results of the quality inspection of the sampled drugs and raw materials;

c) Provide scientific and technical information related to ensuring drug and raw material quality.

Provide the Central Institute of Pharmaceutical Inspection, Ho Chi Minh City Institute of Pharmaceutical Inspection with drug labels and quality standards of drugs and raw materials that have been granted registration certificates or import permits, and updates in case of changes. For vaccines and biological products, the labels and quality standards are transferred to the National Institute of Vaccines and Biologicals;

d) Organize national inspections of the quality of produced, compounded, circulated, and used drugs. Direct and supervise the national drug testing system. Conclude on the quality of drugs based on the results of state drug testing institutions and related documents;

đ) Lead or coordinate in implementing state quality control functions, inspections, and handling of violations of drug quality laws according to their authority.

2. The Department of Health shall be responsible for:

a) Organizing the implementation of drug quality inspections within its jurisdiction and handling violations according to the provisions of the law;

b) Developing plans for sampling drugs and raw materials for inspection and submitting them to the People's Committee of the province or centrally governed city for consideration, approval, and allocation of budget for plan implementation within their authority;

c) Updating information on drug samples and raw materials for inspection into the Ministry of Health's drug quality inspection data system (including information such as drug name, raw material name, concentration, content, dosage form, batch number, expiration date, circulation permit number or import permit, production facility, import facility, sampling facility, and inspection results for drug samples and raw materials);

3. The drug testing system shall be responsible for:

a) Central drug testing facilities (Central Institute of Drug Testing, Ho Chi Minh City Institute of Drug Testing, National Institute of Vaccine and Biological Product Control):

- Conducting analysis and testing of samples to determine the quality of produced, circulated, and used drugs and raw materials; reporting test results to the Ministry of Health (Department of Medicine Management) and the Department of Health where the samples were taken;

- Researching, establishing, and publishing on the electronic information websites of the Institutes and the Department of Medicine Management lists of standards, reference substances, and impurities for the analysis and testing of produced, imported, circulated, and used drugs and raw materials within Vietnam;

- The Central Institute of Drug Testing and Ho Chi Minh City Institute of Drug Testing shall be responsible for providing copies or electronic documents of drug and raw material quality standards to provincial and centrally governed city drug testing centers within their assigned areas;

- The National Institute of Vaccine and Biological Product Control shall review and evaluate vaccine and biological product quality trends annually and submit guidance on testing and issuing certificates for vaccines and biological products containing antibodies derived from blood and plasma to the Ministry of Health for issuance;

Updating information on the issuance of quality certificates for vaccines and biological products containing antibodies derived from blood and plasma on the electronic information websites of the National Institute of Vaccine and Biological Product Control and the Department of Medicine Management;

b) Provincial and centrally governed city drug testing centers:

- Conducting analysis and testing of samples to determine the quality of produced, circulated, and used drugs and raw materials;

- Reporting test results to the Department of Health and the Ministry of Health (Department of Medicine Management);

4. Business entities shall be responsible for:

a) Organizing research and implementation of legal regulations on drug and raw material quality issued in this Circular;

b) Implementing regulations on monitoring the origin and quality of drugs and raw materials. Ensuring quality control activities throughout the operation of the facility to guarantee drug and raw material quality;

c) Establishing documentation systems to track the circulation of drugs and raw materials. Monitoring and supervising the quality of drugs and raw materials sold by businesses; promptly identifying and handling non-compliant drugs and reporting to management and quality control agencies;

5. During the period when quality control officers at all levels have not been appointed, the Ministry of Health shall assign:

a) The Central Institute of Drug Testing, Ho Chi Minh City Institute of Drug Testing, and the National Institute of Vaccine and Biological Product Control, according to their functions, tasks, and scope of operations:

- Developing plans for sampling drugs for quality inspection and supervision; preparing and accepting annual funding for sampling and testing activities;

- Carrying out sampling of drugs and raw materials according to approved plans at pharmaceutical business establishments and drug usage facilities;

- Updating information on sampled drugs and raw materials for quality inspection and test results into the Ministry of Health's drug quality inspection data system;

- Reporting test results to the Ministry of Health (Department of Medicine Management) and the Department of Health where the samples were taken for drugs and raw materials that do not meet quality standards as stipulated in Clause 3, Article 7 of this Circular;

- The Central Institute of Drug Testing shall establish the Ministry of Health's drug quality inspection data system;

b) Provincial and centrally governed city drug testing centers:

- Developing plans for sampling to inspect and monitor drug and raw material quality; preparing and accepting annual funding for sampling and testing activities;

- Carrying out sampling of drugs and raw materials for quality inspection according to approved plans at business and drug usage facilities;

- Updating information on sampled drugs and raw materials for quality inspection and test results into the Ministry of Health's drug quality inspection data system;

- Reporting test results to the Ministry of Health (Department of Medicine Management) and the Department of Health for drugs and raw materials that do not meet quality standards as stipulated in Clause 3, Article 7 of this Circular;

Article 19. Responsibility for Implementation

The Director of the Department of Medicine Management, the Head of the Ministry's Office, the Inspector General of the Ministry, Heads of units under and affiliated with the Ministry of Health, Departments of Health of provinces and centrally governed cities, pharmaceutical business establishments, and other relevant agencies, organizations, and individuals shall be responsible for implementing this Circular;

In the course of implementation, if there are any issues, agencies, organizations, and individuals are advised to report to the Ministry of Health (Department of Medicine Management) for consideration and resolution.