Circular No. 03/2020/TT-BYT amends and supplements certain provisions of Circular No. 11/2018/TT-BYT dated May 4, 2018, of the Minister of Health on the quality of drugs and raw materials for drug production.

CIRCULAR

AMENDING AND SUPPLEMENTING SOME ARTICLES OF THE CIRCULAR NO. 11/2018/TT-BYT DATED MAY 4, 2018 OF THE MINISTER OF HEALTH ON THE QUALITY OF DRUGS AND DRUG INGREDIENTS

2018 OF THE MINISTER OF HEALTH REGULATING THE QUALITY OF DRUGS AND DRUG INGREDIENTS

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 some provisions and measures for implementing the Pharmaceutical Law;

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. 75/2017/NĐ-CP dated June 20the 2017 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 amending and supplementing some articles of Circular No. 11/2018/TT-BYT dated May 4, 2018 of the Minister of Health on the quality of drugs and drug ingredients.

Article 1. Amending and supplementing some articles of Circular No. 11/2018/TT-BYT dated May 4, 2018 of the Minister of Health on the quality of drugs and drug ingredients

1. Amend Article 1 as follows:

"This Circular stipulates the application of drug quality standards (chemical drugs, herbal drugs, vaccines, biological products), drug ingredient standards (including semi-finished products, herbal semi-finished products, except herbal materials); the testing of drugs and drug ingredients and procedures for recalling and handling non-compliant drugs."

2. Amending and supplementing Clause 1, Article 7 as follows:

"1. Applying quality standards in the testing of drugs and drug ingredients:
a) Testing must be carried out according to the approved and updated drug quality standards and drug ingredient standards.

In cases where the drug quality standards and drug ingredient standards have not been updated, the testing facility shall apply the corresponding pharmacopoeia standards as stipulated in Clause 1 and Clause 2, Article 6 of this Circular, based on the production date of the batch of drugs and drug ingredients being tested.

Testing of compounded and formulated drugs at healthcare facilities shall be conducted according to the quality standards established and issued by the facility.

b) In cases where the test methods recorded in the drug quality standards and drug ingredient standards contain errors, do not ensure accuracy, or are non-specific qualitative tests, or herbal drugs suspected of containing additional active substances/chemical substances (drugs with side effects, drugs with unusual effects), or information about drugs and drug ingredients containing impurities from foreign drug regulatory authorities, state drug testing facilities may apply analytical/testing methods specified in the pharmacopoeia or methods that have been validated according to the guidelines for method validation set forth in Appendix I of Circular No. 32/2018/TT-BYT dated November 12, 2018 of the Minister of Health on the registration and circulation of drugs and drug ingredients to conduct testing and issue test results on drug quality. The head of the drug testing facility shall be responsible for the test results of their facility under the law."

3. Amending and supplementing Point c, Clause 3, Article 7 as follows:

"c) Within a maximum period of 20 days from the date of receiving the drug sample, the testing facility must provide the test and analysis results in the following cases:

- Drugs that must be tested before circulation as stipulated in Clause 1, Article 8 of this Circular, except for vaccines and biological products containing antibodies, blood derivatives, and human plasma as stipulated in Clause 2, Article 10 of this Circular.

- Drugs not falling under the cases stipulated in Points b and d of this Clause."

4. Amending Clause 6, Article 7 as follows:

"6. Retaining records and documents:
a) Records and documents related to the quality control of drugs and drug ingredients must be retained in accordance with the Law on Archives, the Decree guiding the Law on Archives, and Circular No. 53/2017/TT-BYT dated December 29, 2017 of the Minister of Health on the retention period for professional and operational records in the health sector.

b) Records and documents that have exceeded the retention period shall be disposed of in accordance with the laws on archives."

5. Amending and supplementing Clause 3, Article 8 as follows:

"3. The Ministry of Health (Department of Drug Management) designates testing facilities that meet Good Laboratory Practice (GLP) to perform the drug testing prescribed in Clause 1 of this Article, including:
a) Testing facilities as stipulated in Clause 1, Article 35 of the Pharmaceutical Law that meet GLP requirements, including state testing facilities that meet GLP requirements;
b) Drug testing service facilities holding a Business Registration Certificate for drug testing services;
c) Testing facilities meeting GLP requirements under Strict Regulatory Authorities (SRA) or designated by such authorities to conduct drug and drug ingredient testing for quality control purposes;
d) National public testing facilities recognized by the World Health Organization (WHO) through the Prequalification program.

In cases where the designated testing facility does not have the necessary conditions to perform one or more tests, the testing facility must notify, seal the sample, and cooperate with the manufacturer or importer to send the sealed sample to another testing facility that meets GLP requirements or a laboratory meeting ISO/IEC 17025 standards and has the necessary conditions to perform these tests."

6. Supplementing Point d, Clause 6, Article 8 as follows:

"d) Selecting testing facilities meeting the requirements of Point a, Clause 3 of this Article to send samples for quality testing. In cases where the testing facility does not have the necessary conditions to perform one or more quality indicators, cooperating with the testing facility to send the sealed sample to another testing facility capable of performing these tests."

7. Amending the title of Clause 2, Article 10 as follows:

"Within a maximum period of 60 days from the date of receipt of sufficient samples and documents as stipulated in Article 11 of this Circular, the National Institute of Vaccines and Biological Products shall proceed with:"

8. Amending and supplementing Point b, Clause 1, Article 11 as follows:

"b) Samples of vaccines and biological products for testing (the quantity of samples for each type of vaccine and biological product, as specified in the Ministry of Health's Guidelines on Testing Before Vaccine and Biological Product Release, which are serum containing antibodies, blood derivatives, and human plasma);"

9. Amend and supplement Point b Clause 2 Article 11 as follows:

"b) Samples of vaccines and biological products for testing (the quantity of samples for each type of vaccine and biological product, as specified in the Ministry of Health's Guidelines on Testing Before Vaccine and Biological Product Release, which are serum containing antibodies, blood derivatives, and human plasma);"

10. Supplement Clause 4 Article 11 as follows:

"4. The summary production and quality control documentation of the batch of vaccines and biological products shall be carried out according to the WHO Model Form No. 09 attached as Appendix III to this Circular."

11. Amend and supplement Article 14 as follows:

"Article 14. Handling of substandard drugs based on sampling location
1. In the case where the drug sample violating standards is taken by the quality control agency from retail drug outlets, level 3 and 4 healthcare facilities (hereinafter referred to collectively as retail outlets):
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 48 hours from the time of receiving the test report or analysis sheet sent by the testing facility, the Ministry of Health (Drug Administration Department) shall issue a document requesting the registration entity, manufacturer, or importer to cooperate with the wholesale distributor:

- To report the distribution situation of the drugs to the wholesale distributors and level 2 and above healthcare facilities (production and import quantities; name, address of the purchasing entity, purchase quantity, and remaining stock at each entity) to be submitted to the Ministry of Health (Drug Administration Department) and the local Department of Health within a maximum period of seven days from the date the Ministry of Health (Drug Administration Department) issues the request document;

- To propose and cooperate with the quality control agency to take additional samples at least two business establishments using the drugs, as stipulated in Clause 4 of this Article, from the manufacturing entity for domestic drugs or the importing entity for imported drugs; submit the report on the implementation results to the Ministry of Health (Drug Administration Department) within a maximum period of fifteen days from the date the Ministry of Health (Drug Administration Department) issues the request document;

- Sending the collected samples to central-level testing facilities for quality control on non-conforming criteria.
c) Based on the test results of the additional drug samples collected, the Drug Administration Department shall handle the matter according to the provisions of Clause 5 of this Article.
2. In the case where the drug sample violating standards is taken by the quality control agency from wholesale distributors, level 2 and above healthcare facilities (hereinafter referred to as wholesale distributors):
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 48 hours from the time of receiving the test report or analysis sheet sent by the testing facility, the Ministry of Health (Drug Administration Department) shall determine the extent of violation and conclude on the recall of the non-compliant drugs according to the provisions in Appendix II issued together with this Circular and issue a document:

- Announcing the recall of the drugs in the province or centrally-administered city where the sample was taken and the business entities and users supplied by the wholesale distributor where the drug sample was taken, according to the provisions of Clauses 3 and 4 of Article 12 of this Circular;

- Requesting the registration entity, manufacturer, or importer to cooperate with the wholesale distributor:

+ To report the distribution situation of the drugs to the wholesale distributors (production and import quantities; name, address of the purchasing entity, purchase quantity, and remaining stock at each entity) to be submitted to the Ministry of Health (Drug Administration Department) and the local Department of Health within a maximum period of seven days from the date the Ministry of Health (Drug Administration Department) issues the document;

+ To propose and cooperate with the quality control agency to take additional samples of at least two drug samples from business establishments using the drugs, as stipulated in Clause 4 of this Article; submit the report on the implementation results to the Ministry of Health (Drug Administration Department) within a maximum period of fifteen days from the date the Ministry of Health (Drug Administration Department) issues the request document;

+ Sending the collected samples to the central-level testing facility for quality testing on non-conforming criteria.
c) Based on the test results of the additional drug samples collected, the Drug Administration Department shall handle the matter according to the provisions of Clause 5 of this Article.
3. In the case where the drug sample is taken by the quality control agency from the manufacturing entity, importing entity, or drug storage service provider, or the drug is determined to violate quality standards due to reasons during the manufacturing process, or when the batch of drugs has been simultaneously sampled from two wholesale distributors, the Ministry of Health (Drug Administration Department) shall determine the extent of violation and conclude on the recall of the non-compliant drugs according to the provisions in Appendix II issued together with this Circular, and issue a decision to recall the drugs according to the provisions of Clause 3 of Article 12 of this Circular. The scope and time limit for the recall shall be implemented according to the provisions of Clause 3 of Article 63 of the Medicine Law.
4. Requirements for taking additional samples for quality testing as stipulated in Clause 1 and Clause 2 of this Article:

The drug quality control agency shall determine the sampling plan based on the distribution reports from the manufacturing entity and the importing entity; prioritize sampling according to the following order a, b, c, d, đ:
a) Samples of drugs taken from wholesale distributors in different provinces and centrally-administered cities, including those that have supplied drugs to the sampled entity;
b) Samples of medicines taken at wholesale facilities in different provinces and cities;
c) Samples of drugs taken from wholesale distributors in the same province or centrally-administered city;
d) Samples of drugs taken from both wholesale distributors and retail outlets.
đ) Samples of drugs taken from retail outlets.
e) Apply sampling according to option đ only if the manufacturing entity or importing entity can prove that the drugs are no longer stored at the wholesale distributors. No additional sampling shall be conducted for the recalled drugs.
5. Handling of the test results of the additional drug samples taken.
a) If the additional drug samples meet quality standards, the Ministry of Health (Drug Administration Department) shall issue a document determining the extent of violation, the responsible entity for the violation, and instruct the Department of Health to handle the drugs from the initial sampled retail outlet in the case stipulated in Clause 1 of this Article, or the wholesale distributor and the recalled drugs in the province or centrally-administered city in the case stipulated in Clause 2 of this Article.

The scope and time limit for the recall shall be implemented according to the provisions of Clause 3 of Article 63 of the Medicine Law;

b) In the case where at least one sample of medicine taken for supplementary testing at a retail establishment does not meet quality standards, except in cases provided for in point a of this Clause, the Ministry of Health (the Drug Administration Department) shall assess the risk, issue a document to determine the level of violation, the entity responsible for the violation, direct the Provincial Health Departments to handle the medicines at the retail establishments from which samples were taken, and warn about the storage conditions and quality of the medicines.

c) In the case where at least one (one) sample of medicine taken for supplementary testing at a wholesale establishment or all samples of medicine taken for supplementary testing at a retail establishment as stipulated in point d of Clause 4 of this Article do not meet quality standards, the Ministry of Health (the Drug Administration Department) shall determine the level of violation and conclude on the recall of the non-compliant medicines according to the provisions in Appendix II issued together with this Circular, and issue a decision to recall the medicines according to the provisions of Clause 3 of Article 12 of this Circular.

12. Supplement point d of Clause 2 of Article 15 as follows:

"d) Fake medicines, smuggled medicines, medicines of unknown origin, expired medicines, medicines containing prohibited substances, medicines produced from substandard raw materials, medicines that must be destroyed according to the regulations set forth in the Decree on administrative penalties in the field of health, and samples of medicines that have exceeded their retention period as prescribed."

13. Amend and supplement Clause 6 of Article 15 as follows:

"6. Destroying medicines:
a) The head of the entity having medicines that need to be destroyed shall issue a decision to establish a Medicines Destruction Committee to organize the destruction process, decide on the method of destruction, and supervise the destruction. The committee must consist of at least three people, including one representative who is the person in charge of the entity's specialized work;

b) The destruction of medicines must ensure safety for people and animals and prevent environmental pollution in accordance with the current laws on environmental protection.

The entity having medicines that need to be destroyed shall bear full responsibility related to the destruction process and must report along with the minutes of the destruction to the Provincial Health Department in accordance with Model Number 06 of Appendix III issued together with this Circular.

c) Regulations on the destruction of vaccines:

- At least seven days before carrying out the destruction of vaccines, the entity destroying the vaccines must submit a written notice of the destruction plan to the Provincial Health Department, including information on the name, quantity, concentration or content of each vaccine to be destroyed, the reason for requesting destruction, the time of destruction, the location of destruction, and the method of destruction. The Provincial Health Department has the responsibility to supervise the destruction of vaccines.

- The process of destroying vaccines and the destruction of vaccines must be carried out in accordance with the current regulations stipulated in Joint Circular No. 58/2015/TTLT-BYT-BTNMT dated December 31, 2015 of the Minister of Health and the Minister of Natural Resources and Environment on the management of medical waste and Circular No. 36/2015/TT-BTNMT dated June 30, 2015 of the Minister of Natural Resources and Environment on the management of hazardous waste.

- Within seven days from the end of the destruction of vaccines, the entity must submit a written report on the destruction of vaccines along with the minutes of the destruction to the Provincial Health Department and the Drug Administration Department. The minutes of the destruction must follow Model Number 06 of Appendix III issued together with this Circular.

d) The destruction of medicines that require special control must be carried out in accordance with the provisions of Article 48 of Decree No. 54/2017/NĐ-CP."

14. Amend and supplement point b and point e of Clause 1 of Article 18 as follows:

"b) Take the lead in coordinating with the Central Institute of Pharmaceutical Inspection, the Ho Chi Minh City Institute of Pharmaceutical Inspection, and the National Institute of Vaccine and Biological Products to develop plans for sampling medicines for quality inspection at production, compounding, import, export, storage, wholesale, retail, and usage facilities nationwide, submit these plans to the Ministry of Health for review and approval, and allocate the budget to implement the plans within their authority.

Implement the sampling of medicines for quality inspection according to the approved plan and update the Ministry of Health's system of quality inspection data for medicines with information on the sampled medicines and raw materials (including information such as the name of the medicine, raw materials, concentration, content, dosage form, batch number, expiration date, registration certificate number or import permit, manufacturing facility, importing facility, sampling facility) and the results of the quality inspection of the sampled medicines and raw materials;"
"e) Take the lead and coordinate with relevant agencies to be responsible for translating, publishing, and updating on the website of the Drug Administration Department the World Health Organization (WHO) guidelines on the destruction of medicines for entities to refer to during the selection of destruction methods and implementation."

15. Amend and supplement point b of Clause 2 of Article 18 as follows:

"b) Develop plans for sampling medicines and raw materials for quality inspection at production, compounding, import, export, storage, wholesale, retail, and usage facilities within the province or city, submit these plans to the People's Committees of provinces and centrally governed cities for review and approval, and allocate the budget to implement the plans within their authority;"

16. Amend and supplement point a of Clause 3 of Article 18 as follows:

"a) Central-level pharmaceutical inspection institutions (Central Institute of Pharmaceutical Inspection, Ho Chi Minh City Institute of Pharmaceutical Inspection, National Institute of Vaccine and Biological Products):

- Conduct analysis and inspection of samples to determine the quality of medicines and raw materials produced, marketed, and used; report the inspection results to the Ministry of Health (Drug Administration Department) and the Provincial Health Departments where the samples were taken;

- Research, establish, and publish on the websites of the Institutes and the Drug Administration Department lists of reference substances, comparison substances, and standard impurities for the analysis and inspection of samples of medicines and raw materials produced, imported, marketed, and used in Vietnam;

- The Central Institute of Pharmaceutical Inspection and the Ho Chi Minh City Institute of Pharmaceutical Inspection are responsible for providing copies or electronic documents of the quality standards of medicines and raw materials to the provincial pharmaceutical inspection centers under their assigned areas."

- The National Institute of Vaccines and Medical Biological Products shall, on an annual basis, review and assess trends in vaccine and medical biological product quality, submit to the Drug Administration for review and promulgation by the Ministry of Health of the Ministry of Health's Guidelines on testing and releasing vaccines and medical biological products containing antibodies, blood derivatives, and human plasma; the contents include:

+ General policies on testing and releasing, including policies on exemptions from testing for vaccines and medical biological products that have been evaluated and issued Batch Release Certificates by Strict Regulatory Authorities (SRA);

+ Testing criteria required for certification of product quality, timeframes for issuing quality certificates for each vaccine and medical biological product; and

+ Sample Summary Production and Quality Inspection Records for batches of vaccines and medical biological products for each type of vaccine and medical biological product.

Update information on the issuance of quality certificates for vaccines and medical biological products containing antibodies and blood derivatives on the electronic website of the Institute and the Drug Administration.

17. Supplement Point a Clause 5 Article 18 as follows:

"Reimburse sampling fees paid by businesses and testing costs for drug samples and raw materials for drugs that do not meet quality standards as prescribed by law."

18. Supplement Point b Clause 5 Article 18 as follows:

"Reimburse sampling fees paid by businesses and testing costs for drug samples and raw materials for drugs that do not meet quality standards as prescribed by law."

19. Amend Item I Appendix I, Clause 8 as follows:

"8. Sampling of medicinal herbs

1. Medicinal herbs or partially processed medicinal herbs, including animals, plants (dried medicinal plants and parts of plants), and minerals, are considered non-uniform raw materials, and sampling shall be conducted according to the provisions at Item I, Clause 9, diagram r of this Appendix.

2. Sampling for monitoring the quality of medicinal herbs by state drug quality inspection agencies: Conducted in accordance with the "Guidelines for Quality Control of Herbal Materials" 2011 of the World Health Organization (Quality control methods for herbal materials 2011). In cases where batches of medicinal herbs are non-uniform, sampling shall be conducted in accordance with the provisions of Point 1 of this Clause."

20. Add Form No. 09 to Appendix III, Summary Production and Quality Inspection Records for batches of vaccines and medical biological products accompanying this Circular.

Article 2. Effective Date

This Circular takes effect from March 16, 2020.

Article 3. Responsibility for Implementation.

The Director of the Drug Administration, the Head of the Ministry's Office, the Inspector General of the Ministry, Heads of units under and affiliated with the Ministry of Health, Provincial and Municipal Health Departments, pharmaceutical business establishments, and other relevant agencies, organizations, and individuals are responsible for implementing this Circular.

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