Integrated document 06/VBHN-BYT 2020 quality of pharmaceutical products and starting materials

• Official number: 06/VBHN-BYT
• Legislation Type: Integrated document
• Organization: The Ministry of Health
• Signer: Truong Quoc Cuong
• Issued Date: 03/07/2020

MINISTRY OF HEALTH --------	THE SOCIALIST REPUBLIC OF VIETNAM Independence - Freedom - Happiness ---------------
No. 06/VBHN-BYT	Hanoi, July 03, 2020

CIRCULAR

QUALITY OF PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING MATERIALS

The Circular No. 11/2018/TT-BYT dated May 04, 2018 of the Minister of Health on quality of pharmaceutical products and pharmaceutical starting materials, which comes into force from June 20, 2018, is amended by:

Circular No. 03/2020/TT-BYT dated January 22, 2020 of the Minister of Health on amendments to some Articles of the Circular No. 11/2018/TT-BYT dated May 04, 2018 of the Minister of Health on quality of pharmaceutical products and pharmaceutical starting materials (hereinafter referred to as “the Circular No. 03/2020/TT-BYT”), which comes into force from March 16, 2020.

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

Pursuant to the Government’s Decree No. 54/2017/ND-CP dated May 08, 2017 on guidelines for the implementation of the Law on Pharmacy;

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

At the request of the Director General of the Drug Administration of Vietnam,

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Chapter I

GENERAL

Article 1. Scope2This Circular provides for application of quality standards for pharmaceutical products (modern pharmaceutical products, herbal materials, vaccines and biologicals) and pharmaceutical starting materials (including semi-finished and finished ones, excluding herbal materials); pharmaceutical product and pharmaceutical starting material tests and procedures for recall and handling of violating pharmaceutical products.

Article 2. Definitions

For the purposes of this Circular, the terms below shall be construed as follows:

1. “pharmaceutical product and pharmaceutical starting material quality standard” refers to a document regulating technical characteristics of pharmaceutical products and pharmaceutical starting materials, including quality criteria, quality levels, test methods and other administrative requirements.

2. “GLP” stands for Good Laboratory Practice.

3. “WHO” stands for World Health Organization.

4. “ICH” stands for International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.

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APPLICATION OF PHARMACEUTICAL PRODUCT AND PHARMACEUTICAL STARTING MATERIAL QUALITY STANDARDS

Article 3. General

1. Pharmacy business establishments and pharmaceutical product preparing facilities shall apply pharmaceutical product and pharmaceutical starting material quality standards by way of pharmacopeia or internal standards for pharmaceutical products and pharmaceutical starting materials produced and prepared by those facilities.

2. Pharmacy business establishments and pharmaceutical product preparing facilities must carry out validation and assessment of test methods stated in pharmaceutical product/pharmaceutical starting material quality standards published and applied by the manufacturers. Validation and assessment of test methods shall be carried out in accordance with ASEAN or ICH guidelines for validation of analytical procedures specified in the Circular on marketing authorization of pharmaceutical products and pharmaceutical starting materials promulgated by the Minister of Health.

3. The Ministry of Health shall organize document appraisal and approval of pharmaceutical product/pharmaceutical starting material quality standards in accordance with regulations on marketing authorization of pharmaceutical products and pharmaceutical starting materials and on issuance of licenses to import pharmaceutical products and pharmaceutical starting materials that are yet to be approved for marketing authorization.

Article 4. Application of pharmacopeia

1. Application of Vietnam’s pharmacopeia and reference pharmacopeias:

a) Pharmacy business establishments and pharmaceutical product preparing facilities can apply Vietnam’s pharmacopeia or one of the following reference pharmacopeias: European, British, United States, International, and Japanese;

b) The application of standards of the pharmacopeias specified in Point a of this Clause must include all regulations on quality criteria, quality levels and test methods specified in the respective import pharmaceutical product/pharmaceutical starting material’s treatise in the chosen pharmacopeia; also include regulations on quality criteria, quality levels and general test methods specified in the Appendix of that pharmacopeia;

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d) For herbal medicinal products, pharmacy business establishments and pharmaceutical product preparing facilities can apply the pharmacopeias specified in Point a of this Clause or the pharmacopeia of the pharmaceutical product’s country of origin.

2. Application of pharmacopeias other than those specified in Point a Clause 1 of this Article:

If the pharmacy business establishment or pharmaceutical product preparing facility decides to apply a pharmacopeia other than that specified in Point a of this Clause, the applied quality standards must at least:

a) Meet the requirements of quality criteria and levels specified in the respective quality criteria’s treatises in Vietnam’s pharmacopeia or one of the aforementioned reference pharmacopeias;

b) The applied common test methods must be appropriate for the equivalent common test methods stated in Vietnam’s pharmacopeia or one of the reference pharmacopeias specified in Point a Clause 1 of this Article.

Article 5. Application of internal standards

1. The internal pharmaceutical product/pharmaceutical starting material quality standards must conform to the regulations specified in Point b Clause 2 Article 102 of the Law on Pharmacy. To be specific:

a) The requirements for quality criteria and levels specified in the respective treatises in Vietnam’s pharmacopeia and quality criteria, quality levels and common test methods specified in the appendices to Vietnam’s pharmacopeia are satisfied;

b) If Vietnam's pharmacopeia or the reference pharmacopeias specified in Point a Clause 1 Article 4 of this Circular do not have any treatise for the required pharmaceutical product/pharmaceutical starting material, the facility shall establish the standard using the scientific research results (also including the product development research results) or the regulations in other foreign pharmacopeias as the basis.

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Article 6. Updating of quality standards and application of updated pharmacopeia

1. When applying for marketing authorization (or renewal of the marketing authorization) of a pharmaceutical product/pharmaceutical starting material: the quality standards for that pharmaceutical product/pharmaceutical starting material must conform to one of the following pharmacopeias at the time of application:

a) The pharmacopeia’s latest edition;

b) The pharmacopeia’s previous editions which did not come more than two years before the current edition.

2. In the case of pharmaceutical products or pharmaceutical starting materials which have been approved for market authorization: For a maximum of two years from the effective date of the pharmacopeia’s latest edition, the applicant or manufacturer has the responsibility to update the standards for pharmaceutical products/pharmaceutical starting materials as regulated by that edition.

3. During the marketing authorization of pharmaceutical product/pharmaceutical starting material, if the applicant or manufacturer finds any factor that severely affects pharmaceutical product safety, quality or efficacy or is requested by the Ministry of Health (Drug Administration of Vietnam), the manufacturer must the update the pharmaceutical product/pharmaceutical starting material quality standards’ criteria in order to bring that factor under control.

Chapter III

PHARMACEUTICAL PRODUCT/PHARMACEUTICAL STARTING MATERIAL TESTS

Article 7. Pharmaceutical product/pharmaceutical starting material tests

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a) The test must be carried out in accordance with the approved and updated pharmaceutical product/pharmaceutical starting material quality standards.

If the pharmaceutical product/pharmaceutical starting material quality standard is yet to be updated, the testing facility shall use the equivalent pharmacopeia specified in Clauses 1 and 2 Article 6 of this Circular, based on the production date of the pharmaceutical product/pharmaceutical starting material quality standard being tested.

If the pharmaceutical product is prepared in a health facility, the test is carried out in accordance with the pharmaceutical product quality standards formed and promulgated by the facility.

b) If a testing method specified in the pharmaceutical product/pharmaceutical starting material quality standard contains errors, thereby failing to ensure the accuracy or trueness or a qualitative test is non-specific or an herbal medicinal product to which the addition of an active ingredient/chemical substance is suspected (the pharmaceutical product has side effects or unreported side effects, or foreign pharmaceutical regulatory agencies inform that the pharmaceutical product/pharmaceutical starting material contains impurities, the state-owned pharmaceutical product testing facility is entitled to apply the analytical/testing methods specified in the pharmacopoeia or validated according to the guidelines on analytical method validation enclosed with the Circular No. 32/2018/TT-BYT dated November 12, 2018 of the Minister of Health. The head of the pharmaceutical product testing facility shall be responsible to the law for its test results.

2. The collection of pharmaceutical product/pharmaceutical starting material samples for testing is carried out in accordance with Appendix I and the sample collection form in Template No. 1 of Appendix III issued together with this Circular.

3. Presenting pharmaceutical product/pharmaceutical starting material test/analysis results:

a) The pharmaceutical product/pharmaceutical starting material test and analysis results are shown on the test/analysis report based on Samples No. 2 and No. 3 shown in Appendix III issued together with this Circular;

b) The testing facility must present the test/analysis results of the pharmaceutical product sample, which was collected by the quality inspection authority within 15 days after receiving the pharmaceutical product sample in the following cases:

- There is information on severely adverse effects of the pharmaceutical product;

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- Additional samples of the pharmaceutical product are collected in the cases mentioned in Point b Clause 1 and Point b Clause 2 Article 14 hereof.

 c)4The testing facility must present the test/analysis results of the pharmaceutical product sample within 20 days after receiving it in the following cases:

- The pharmaceutical product requires testing before marketing as specified in Clause 1 Article 8 of this Circular, except for the vaccine or biological that is serum containing antibodies and derivatives of human blood and plasma as specified in Clause 2 Article 10 of this Circular.

- The pharmaceutical product does not fit any of the cases mentioned in Points b and d of this Clause.

d) The testing facility must present the test/analysis results of the pharmaceutical product/pharmaceutical starting material sample within 30 days after receiving it in the following cases:

- The pharmaceutical product/pharmaceutical starting material has test methods that require long testing time;

- The pharmaceutical product/pharmaceutical starting material requires re-validation or reevaluation of test results;

- The pharmaceutical product/pharmaceutical starting material has dubious contents or quality, which require test methods other than the ones stated in the registered quality criteria;

- The pharmaceutical product/pharmaceutical starting material requires test methods that the testing facility is incapable of conducting (e.g. lack of equipment, chemical, reagents, reference materials).

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e) Within 24 hours from the time the test/analysis report is issued, the testing facility must send the form to the quality inspection authority, the facilities producing or importing the pharmaceutical product/pharmaceutical starting material being tested on and the facility where the sample was taken from.

If the pharmaceutical product/pharmaceutical starting material sample does not meet the quality standards, within 24 hours from the time the test/analysis report is issued, the testing facility must notify the Ministry of Health (Drug Administration of Vietnam) of that sample in writing with the test/analysis report attached, both physical and electronic copies (the latter, which is scanned, can be sent to the email address [e-mail] or via messaging to the Drug Administration's phone number, with both methods of correspondence using the testing facility's official email address and phone number). A similar notification must also be sent to the Department of Health whose jurisdiction is where the tested pharmaceutical product/pharmaceutical starting material comes from.

g) In the case of the pharmaceutical product/pharmaceutical starting material sample is sent by a pharmacy business establishment, a facility using it, an organization or an individual for analysis, testing or pharmaceutical product/pharmaceutical starting material quality standard assessment, the time of result presentation shall be agreed upon by the parties.

4. Filing and handling of complaints about test results:

a) If there is disagreement with the sample’s test results, within five days from the date on which the test results are received, the pharmacy business establishment has the right to request the quality inspection authority to assign another testing facility to carry out pharmaceutical product/pharmaceutical starting material quality tests/analyses;

b) Re-testing of quality criteria about which a complaint is filed shall be carried out at the testing facility designated by the Ministry of Health as specified in Clause 2 Article 105 of the Law on Pharmacy.

5. Retention of samples:

a) The pharmaceutical product/pharmaceutical starting material sample must be retained after testing and quality conclusion. The retained sample must be sealed up and preserved as specified in the conditions on the label.

b) Sample retention period:

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- In the case of pharmaceutical product testing facilities: the sample retention period is at least 12 months after the pharmaceutical product’s expiry date, or 24 months after the sample collection date for pharmaceutical product samples collected for quality inspection; or after the date of receipt for additional collected samples specified in Point b Clause 1 and Point b Clause 2 Article 14 of this Circular.

6[2]. Archiving records and documents:

a) The records and documents on pharmaceutical product/pharmaceutical starting material quality inspection must be archived as specified in the Law on Archives, Decrees elaborating the Law on Archives and Circular No. 53/2017/TT-BYT dated December 29, 2017 of the Minister of Health.

b) After the end of their archiving periods, the records and documents shall be handled in accordance with regulations of the Law on Archives.

Article 8. Pre-marketing test for pharmaceutical products specified in Clause 4 Article 103 of the Law on Pharmacy

1. Pharmaceutical products that belong to one of the following categories must undergo testing carried out by a testing facility designated by the Ministry of Health (Drug Administration of Vietnam) before marketing:

a) The pharmaceutical products specified in Points a and b Clause 4 Article 103 of the Law on Pharmacy;

b) Biologicals which are derivatives of human blood and plasma;

c) Imported pharmaceutical products specified in the Government’s Decree No. 54/2017/ND-CP;

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2. Regulations on pharmaceutical product quality tests:

a) Pharmaceutical product sample collection:

- The samples of the pharmaceutical products specified in Points a, b and c Clause 1 of this Article shall be collected by manufacturers (in case of domestic pharmaceutical products) or importers (in case of imported pharmaceutical products);

- The facilities importing the pharmaceutical products specified in Point d Clause 1 of this Article shall request the state’s quality inspection or testing authority to collect samples of those pharmaceutical products.

b) The importer shall send the pharmaceutical product sample alongside a copy of the producer’s test report to the testing facility specified in Clause 3 of this Article for pharmaceutical product quality inspection in accordance with the approved pharmaceutical product quality standards;

c) Facilities producing or importing vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma mentioned in Points a and b Clause 1 of this Article shall send the sample as specified in Articles 10 and 11 of this Circular;

d) The testing facility must present the received sample’s test results within the time limit specified in Point c Clause 3 Article 7 of this Circular.

3[3]. The Ministry of Health (Drug Administration of Vietnam) shall designate GLP-compliant testing facilities to carry out pharmaceutical product tests specified in Clause 1 of this Article, including:

a) GLP-compliant testing facilities specified in Article 1 Article 35 of the Law on Pharmacy, including state-owned ones;

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c) GLP-compliant testing facilities affiliated to SRA - Stringent Regulatory Authorities or designated by these authorities to carry out pharmaceutical product/pharmaceutical starting material tests to serve pharmaceutical product quality management;

d) National public testing facilities that prequalified and published by WHO according to the pharmaceutical product testing laboratory prequalification program.

If the testing facility does not have sufficient capacity for carrying out one or multiple tests, the testing facility must notify the producer/importer and cooperate with the latter in sending samples to other GLP-compliant testing facilities or ISO/IEC 17025 compliant laboratories which have capacity for carrying out those tests.

4. The designated testing facility shall report pharmaceutical product testing to the Ministry of Health (Drug Administration of Vietnam) on a monthly basis, following Template No. 7 of Appendix III issued together with this Circular.

5. The Ministry of Health (Drug Administration of Vietnam) shall publish and update the list of designated testing facilities mentioned in Clause 3 of this Article on the Drug Administration’s website.

6. The producer/importer has the responsibility to:

a) Pay expenses for tests for quality of its pharmaceutical products;

b) Provide reference materials (including those of impurities) to the testing facility if the National Institute of Drug Quality Control, the Institute of Drug Quality Control Ho Chi Minh City, the National Institute for Control of Vaccines and Biologicals or other testing facilities fail to establish;

c) Market and distribute the pharmaceutical products only after their test results show conformity to quality standards.

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7. Tests on vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma are carried out in accordance with Articles 10 and 11 of this Circular.

Article 9. Testing periods for facilities on the list of manufacturers with pharmaceutical products that do not conform to quality standards and withdrawal from that list

1. The testing period starts from the first pharmaceutical product batch's import date after the Ministry of Health (Drug Administration of Vietnam) publishes the list of manufacturers with pharmaceutical products that do not conform to quality standards and lasts:

a) 06 months for the manufacturer having one pharmaceutical product batch with third-degree violation;

b) 12 months for the manufacturer having one pharmaceutical product batch with second-degree violation or 02 or more pharmaceutical product batches with third degree or more serious violations;

c) 24 months for the manufacturer having one pharmaceutical product batch with first-degree violation or 02 or more pharmaceutical product batches with second degree or more serious violations;

d) If the manufacturer continues having violating pharmaceutical products, the total testing period shall be the sum of individual pharmaceutical products’ periods.

2. A manufacturer will be withdrawn from the list of manufacturers with pharmaceutical products that do not conform to quality standards after meeting the following requirements:

a) The manufacturer completes all pharmaceutical product tests before marketing within the time limit specified in Clause 1 of this Article;

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c) The manufacturer has no pharmaceutical product quality violation (including voluntary pharmaceutical product recall due to quality) during the implementation of Clause 1 of this Article.

3. On a monthly basis, the Ministry of Health (Drug Administration of Vietnam) shall publish and update the list of manufacturers with pharmaceutical products that do not conform to quality standards, drop the names of facilities complying with the regulations in Clause 2 of this Article from the list based on reports from testing facilities that participate in testing activities, pharmaceutical product manufacturers and registrants.

Article 10. Test on vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma

1. The producer/importer must send the samples and production records of vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma to the National Institute for Control of Vaccines and Biologicals for testing and evaluation before marketing. The sample sending documents are specified in Article 11 of this Circular.

The producer/importer is allowed to only market or use vaccines, biologicals which are antisera, derivatives of human blood and plasma after the National Institute for Control of Vaccines and Biologicals confirms the vaccine/biological batches' quality, safety and efficacy and issues quality certificates.

2.[4] Within 60 days from the date on which all samples and documents specified in Article 11 of this Circular are received, the National Institute for Control of Vaccines and Biologicals shall:

a) Review the records and conduct tests on the vaccine/biological samples received;

b) Issue quality certificates which follow Template No. 08 of Appendix III issued under this Circular, in which the requirements that are met and which requirements are not, alongside conclusions on the vaccine/biological batch's quality, safety and efficacy;

c) Notify the Ministry of Health (Drug Administration of Vietnam) of the test results.

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1. For local vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma: The manufacturer shall send the production records and samples from the product batches (either finished or semi-finished products) to the National Institute for Control of Vaccines and Biologicals, including:

a) The sample sending form;

b) 9 The vaccine/biological samples to be tested on (the number of samples for each kind of vaccine/biological is specified in the Guidelines of the Ministry of Health for lot release testing of vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma);

c) The lot summary protocols (copies certified by the manufacturer);

d) The manufacturer’s batch test report.

2. For imported vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma: The importer shall send the production records and samples from the product batches to the National Institute for Control of Vaccines and Biologicals, including:

a) The sample sending form;

b)10 The vaccine/biological samples to be test on (the number of samples for each kind of vaccine/biological is specified in the Guidelines for testing finished vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma);

c) The lot summary protocols (copies certified by the manufacturer or importer);

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dd) The table of data on preservation conditions (cold storage) during the imported batch’s transport (certified by the importer) from automatic temperature recorders, freeze indicators (if any).

3. The manufacturer and importer must be responsible for their documents' legality.

4.[5] The lot summary protocols shall be made according to WHO guidelines provided in the Form No. 09 in the Appendix II hereof.

Chapter IV

REGULATIONS ON RECALL AND HANDLING OF VIOLATING PHARMACEUTICAL PRODUCTS

Article 12. Compulsory pharmaceutical product recall procedure

1. Receiving information on violating pharmaceutical products:

The Ministry of Health (Drug Administration of Vietnam) receives information on violating pharmaceutical products as follows:

a) Information on pharmaceutical products that do not guarantee effective treatment or is unsafe from the pharmaceutical product registration advisory board or post-vaccination complication handling advisory board;

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c) Information on discovered violating pharmaceutical products from the Drug Administration of Vietnam, health/pharmaceutical inspection authority;

d) Violating foreign pharmaceutical product notices from manufacturers, pharmaceutical regulatory agencies and pharmaceutical product quality inspection authorities;

dd) Information on violating pharmaceutical products from public security, customs and market surveillance;

e) Pharmaceutical product information from pharmacy business establishments requesting voluntary pharmaceutical product recall.

2. Identification of the violation’s seriousness:

a) Within 24 hours from the time the information on violating pharmaceutical products mentioned in Points a, c, d, dd and e Clause 1 of this Article, the Ministry of Health (Drug Administration of Vietnam) shall identify the violation’s seriousness and draw conclusions on pharmaceutical product recall, based on evaluation of consumer health's risks.

If the pharmaceutical product registration advisory board's opinion is requested for identification of the violation’s seriousness as specified in Section IV, Appendix II issued together with this Circular, the time limit of identification of violation's seriousness will be 7 days.

b) The seriousness of a pharmaceutical product’s violation is specified in Appendix II issued together with this Circular;

c) For information on violating pharmaceutical products mentioned in Point b Clause 1 of this Article, the handling shall be carried out in accordance with Article 14 of this Circular.

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a) Within 24 hours from the time the conclusion on pharmaceutical product recall is drawn, the Ministry of Health (Drug Administration of Vietnam) shall issue the pharmaceutical product recall decision in accordance with Clause 1 Article 65 of the Law on Pharmacy;

b) The pharmaceutical product recall decision must include the following information: pharmaceutical product name, marketing authorization number or import license number, name of active ingredient, concentration, content, dosage form, batch number, expiry date, manufacturer, importer, recall level, the facility responsible for pharmaceutical product recall.

4. Notification of pharmaceutical product recall decision:

a) The pharmaceutical product recall decision of the Ministry of Health (Drug Administration of Vietnam) is announced by post, fax, email, telephone or the mass media. The scope of pharmaceutical product recall announcement is specified in Clause 3 Article 63 of the Law on Pharmacy;

b) Immediately after making the recall decision, the Ministry of Health (Drug Administration of Vietnam) shall announce the pharmaceutical product recall decision on websites of the Ministry of Health and the Drug Administration of Vietnam, and the Ministry of Health’s national pharmaceutical database;

Departments of Health shall announce pharmaceutical product recall decisions on their websites immediately after receiving those decisions.

Domestic pharmaceutical product manufacturers and importers must notify the information about recalled pharmaceutical products to pharmaceutical product traders/users which purchased those pharmaceutical products.

c) For recalling pharmaceutical products with first-degree violations, besides carrying out the actions specified in Point b of this Clause, the Ministry of Health must announce the pharmaceutical products recall decision on Vietnam Television and Voice of Vietnam.

5. Recalling pharmaceutical products:

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b) The manufacturer (of domestic pharmaceutical products) and importer shall cooperate with the import entrustor or distribution hub (of imported pharmaceutical products) in recalling violating pharmaceutical products. The recall form follows Template No. 4 of Appendix III issued together with this Circular.

The drug trader/provider that fails to recall pharmaceutical products or receive returned pharmaceutical products shall be notified by facilities and individuals purchasing those pharmaceutical products to the local Department of Health and face actions.

c) Pharmaceutical product recall has to be completed within one of the time limits specified in Clause 3 Article 63 of the Law on Pharmacy.

6. Pharmaceutical product recall report, evaluation and additional measures:

a) In 01 day (for first-degree recalls) or 03 days (for second- and third-degree recalls) from the recall’s date of completion, the facility in charge of recalling must report the results to the Ministry of Health (Drug Administration of Vietnam) and the local Department of Health in writing. The report consists of the following documents:

- Summary pharmaceutical product recall report, which follows Template No. 5 of Appendix III issued together with this Circular;

- List of pharmaceutical product traders/users (including those receiving pharmaceutical products from the facility in charge of recalling violating pharmaceutical products, or from distributors) with their addresses, phone numbers, email addresses (if any), amount of pharmaceutical products received, amount of pharmaceutical products recalled;

- Delivery reports, receipts of return or other evidence of pharmaceutical product recall;

- Pharmaceutical product recall self-evaluation form;

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b) The Ministry of Health (Drug Administration of Vietnam) shall consider the report mentioned in Point a of this Clause, evaluate it or send it to the Department of Health for evaluation. If the pharmaceutical product recall is evaluated to be insufficient and the product can still be marketed and used, posing a risk to the consumers' health, the Drug Administration of Vietnam shall cooperate with the Department of Health and other related authorities in coercive pharmaceutical product recall.

Article 13. Voluntary pharmaceutical product recall procedure

1. The pharmacy business establishment that carries out voluntary pharmaceutical product recall shall evaluate and identify the seriousness of the pharmaceutical product's violation and report the violating pharmaceutical product, seriousness of violation, reason for recall and proposed handling measures to the Ministry of Health (Drug Administration of Vietnam) in writing as specified in Clauses 3 and 4 Article 15 of this Circular.

2. Within three days from the date the pharmacy business establishments’ report is received, the Ministry of Health (Drug Administration) consider the report and identify the seriousness of the pharmaceutical product's violation as specified in Appendix II issued together with this Circular.

a) If an agreement with the pharmacy business establishment’s proposal concerning the pharmaceutical product with third-degree violation is reached, the Ministry of Health (Drug Administration of Vietnam) shall send an document allowing the facility to voluntarily recall the pharmaceutical product.

b) In the case of pharmaceutical products with first- or second-degree violations, the Ministry of Health (Drug Administration of Vietnam) shall follow the pharmaceutical product recall procedures mentioned in Clauses 3, 4, 5 and 6 Article 12 of this Circular;

c) If additional information or clarification of information in the pharmacy business establishment’s report is needed, the Ministry of Health (Drug Administration of Vietnam) shall request the establishment to provide additional information and explanations in writing. Within 05 days from the day the Ministry of Health’s request is received, the establishment must provide additional information and explanations in writing.

3. Within 24 hours from the time the Ministry of Health (Drug Administration of Vietnam) shall issue the document allowing voluntary pharmaceutical product recall, the establishment can issue the pharmaceutical product recall decision, notify it to traders/users and carry out pharmaceutical product recall as specified in Clauses 5 and 6 Article 12 of this Circular.

Article 14. Handling of pharmaceutical products not meeting quality standards by place of collection1^2

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a) Within 24 hours from the time the testing facility’s test/analysis report is received, the Department of Health shall seal the substandard pharmaceutical products at the facility where the samples were collected from;

b) Within 48 hours from the time the testing facility’s test/analysis report is received, the Ministry of Health (Drug Administration of Vietnam) request shall request the responsible pharmaceutical product registrant/producer/importer in writing to cooperate with the distributor in:

- reporting its pharmaceutical distribution to wholesalers, health facilities at level II or higher (number of pharmaceutical products manufactured and imported; name and address of the pharmaceutical product purchasers, number of pharmaceutical products purchased and number of pharmaceutical products in stock) to the Ministry of Health (Drug Administration of Vietnam) and Department of Health within 07 days from the date on which the written request is made;

- requesting and cooperating with quality inspection authorities to collect additional samples from domestic pharmaceutical product manufacturers or importers, and from at least 02 pharmaceutical product trading establishments as prescribed in Clause 4 of this Article; sending a report thereon to the Ministry of Health (Drug Administration of Vietnam) within 15 days from the date on which the written request is made;

- sending samples to central testing facilities in order to have the unfulfilled criteria tested.

c) According to the result of testing of additional samples, the Drug Administration of Vietnam shall follow the instructions provided in Clause 5 of this Article.

2. In the case of violating pharmaceutical product samples collected by quality inspection authorities from wholesalers, level-II or above health facilities (hereinafter referred to as “wholesalers”):

a) Within 24 hours from the time the testing facility’s test/analysis report is received, the Department of Health shall seal the substandard pharmaceutical products at the facility where the samples were collected from;

b) Within 48 hours from the time the testing facility’s test/analysis report is received, the Ministry of Health (Drug Administration of Vietnam) shall identify the violation’s seriousness and draw the conclusion on recalling the violating pharmaceutical product as specified in Appendix II issued together with this Circular, and shall:

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- request the responsible registrant, producer or importer in writing to cooperate with the distributor in:

+ reporting its pharmaceutical distribution to wholesalers (number of pharmaceutical products imported; name and address of the pharmaceutical product purchasers, number of pharmaceutical products purchased and number of pharmaceutical products in stock) to the Ministry of Health (Drug Administration of Vietnam) within 07 days from the written request is made;

+ requesting and cooperating with quality inspection authorities to collect additional samples from domestic pharmaceutical product manufacturers or importers as prescribed in Clause 4 of this Article; sending a report thereon to the Ministry of Health (Drug Administration of Vietnam) within 15 days from the date on which the written request is made;

+ sending samples to central testing facilities in order to have the unfulfilled criteria tested.

c) According to the result of testing of additional samples, the Drug Administration of Vietnam shall follow the instructions provided in Clause 5 of this Article.

3. If the sample was collected by a quality inspection authority from manufacturers, importers and preservation service providers, or the sample's quality violation is identified to be caused by the production process, or samples of the same pharmaceutical product batch are collected from 02 wholesalers, the Ministry of Health (Drug Administration of Vietnam) shall identify the violation’s seriousness and draw the conclusion on recalling the violating pharmaceutical product as specified in Appendix II issued together with this Circular, and issue the pharmaceutical product recall decision as specified in Clause 3, Article 12 of this Circular. The recall's scope and time limit are specified in Clause 3 Article 63 of the Law on Pharmacy.

4. Requirements for collecting additional samples for quality testing as prescribed in Clauses 1 and 2 of this Article:

The pharmaceutical product quality inspection authority shall determine a sampling method according to the report on distribution by manufacturers and importers; pharmaceutical product samples shall be collected from wholesalers and retailers in the following order of priority a, b, c, d and dd:

a) From wholesalers within different provinces and cities, including the wholesalers that provided pharmaceutical products to the facilities from which samples were collected;

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c) From wholesalers within the same provinces and cities;

d) From wholesalers and retailers;

dd) From retailers.

e) Samples shall be only collected adopting the method dd if manufacturers and importers prove that pharmaceutical products are no longer stored at wholesalers. Additional samples of recalled pharmaceutical products shall not be collected.

5. Handling of results of testing of additional samples.

a) If the additional samples meet quality standard, Ministry of Health (Drug Administration of Vietnam) shall issue a document identifying the violation’s seriousness and facility responsible for the violation and direct provincial Departments of Health to handle pharmaceutical products of the first retailers from which samples were collected in the case specified in Clause 1 of this Article or wholesalers and recalled pharmaceutical products within provinces and cities in the case specified in Clause 2 of this Article.

The recall's scope and time limit are specified in Clause 3 Article 63 of the Law on Pharmacy;

b) If at least 01 (one) additional sample collected at retailers fails to meet the quality standards, except for the case specified in Point a of this Clause, the Ministry of Health (Drug Administration of Vietnam) shall identify the violation’s seriousness and facility responsible for the violation, direct the provincial Department of Health to handle pharmaceutical products at retailers from which the samples were collected and issue a warning about the pharmaceutical product storage conditions and quality.

c) If at least 01 (one) additional sample collected at wholesalers or all additional samples are collected at retailers as prescribed in Point dd Clause 4 of this Article fail to meet the quality standards, the Ministry of Health (Drug Administration of Vietnam) shall identify the violation’s seriousness and draw the conclusion on recalling the violating pharmaceutical product as specified in Appendix II issued together with this Circular, and issue the pharmaceutical product recall decision as specified in Clause 3 Article 12 of this Circular.

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1. The recalled pharmaceutical product can either be rectified or re-exported if it has third-degree violation and does not fall into the type of pharmaceutical product mentioned in  Point b Clause 2 of this Article.

2. The recalled pharmaceutical product must be destroyed if it has:

a) First- or second-degree violation;

b) Third-degree violation, considered by the Ministry of Health (Drug Administration of Vietnam) to be neither rectifiable nor re-exportable as specified by Clauses 3 and 4 of this Article;

c) Third-degree violation, considered by the Ministry of Health (Drug Administration of Vietnam) to be rectifiable or re-exportable, but the facility fails to rectify or re-export that pharmaceutical product.

d)13 The pharmaceutical product is counterfeit, illegally imported, of unknown origins, expired, composed of banned substances, produced from raw materials that fail to meet quality standards or required to be recalled as prescribed in the Decree on administrative penalties for violations against regulations on health or its stored samples are unexpired.

3. Procedure for proposing rectification of recalled pharmaceutical products:

a) The facility that has recalled pharmaceutical products shall send the Ministry of Health (Drug Administration of Vietnam) a document stating the rectification process, pharmaceutical products quality and stability risk assessment, the program for monitoring and surveillance of the pharmaceutical product’s quality, safety and efficacy during marketing.

b) Within 60 days from the date the facility’s rectification proposal is received, the Ministry of Health (Drug Administration of Vietnam) must consider the proposal and reply their agreement or disagreement in writing. The reason for disagreement must be specified;

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4. Procedure for proposing re-export of recalled pharmaceutical products:

a) The facility that has recalled pharmaceutical products shall send the Ministry of Health (Drug Administration of Vietnam) a document with the re-export plan, stating the time and re-export country;

b) Within 15 days from the date the facility’s proposal is received, the Ministry of Health (Drug Administration of Vietnam) shall reply their agreement or disagreement on the re-export in writing; the reason for disagreement must be specified.

5. The rectification and re-export of recalled pharmaceutical products shall only be carried out after the written agreement of the Ministry of Health (Drug Administration of Vietnam) is issued.

6.[6] Pharmaceutical product destruction:

a) The head of the facility that has pharmaceutical products to be destroyed shall decide to form the pharmaceutical product destruction council responsible for organizing the destruction, deciding destruction methods and supervising the destruction. The council shall have at least 03 persons, with one representative having professional responsibility;

b) Pharmaceutical product destruction must be safe for both humans and animals, does not pollute the environment in accordance with regulations of law on environmental protection.

The facility that has pharmaceutical products to be destroyed shall take total responsibility for the destruction and submit a pharmaceutical product destruction report enclosed with a destruction record to the local Department of Health in accordance with the Form No. 06 in the Appendix III hereof.

c) Vaccine destruction:

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- Vaccine destruction procedures and vaccine destruction shall comply with regulations of the Joint Circular No. 58/2015/TTLT-BYT-BTNMT dated December 31 of the Minister of Health and Minister of Natural Resources and Environment and Circular No. 36/2015/TT-BTNMT dated June 30, 2015 of the Minister of Natural Resources and Environment.

- Within 07 days from the end of the vaccine destruction, the facility shall submit a vaccine destruction report enclosed with a destruction record to the local Department of Health and Drug Administration of Vietnam. The destruction record shall be made using the Form No. 06 in the Appendix III hereof.

d) The destruction of controlled pharmaceutical products shall comply with Article 48 of the Decree No. 54/2017/ND-CP.

7. The recalled pharmaceutical product handling period shall not exceed 12 months from the recall’s date of completion, as specified in Points a, b and c Clause 3 Article 63 of the Law on Pharmacy.

Article 16. Responsibilities for pharmaceutical product recall

1. Responsibilities of pharmacy business establishments, health facilities and pharmaceutical product users:

a) Comply with the regulations in Clauses 1, 2 and 3, Article 64 of the Law on Pharmacy;

b) Regularly review and update information on pharmaceutical product recall from websites of the Ministry of Health, the Drug Administration, and Departments of Health.

2. Responsibilities of the Drug Administration:

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b) Announce pharmaceutical product recall decisions as specified in Point a Clause 4 Article 12 of this Circular, publish information about recalled pharmaceutical products on websites of the Ministry of Health and the Drug Administration after those decisions are issued. Cooperate with Vietnam Television and Voice of Vietnam in announcing recall of pharmaceutical products with first-degree violations;

c) Consider the evaluation reports and reply to the pharmacy business establishments’ proposals for voluntary pharmaceutical product recall, rectification or re-export of recalled pharmaceutical products;

d) Cooperate with related units (Ministry Inspectorate, Department of Health, health divisions of other agencies) in inspection of organization and execution of pharmaceutical product recall; take actions against violating facilities in accordance with the regulations of law;

dd) Produce documents providing detailed guidelines for the processes of pharmaceutical product recall and handling, evaluation of pharmaceutical product recall in pharmaceutical product manufacturers and pharmacy business establishments.

3. Responsibilities of Departments of Health:

a) Publish pharmaceutical product recall decisions on websites of the Departments of Health;

b) Organize announcement and dissemination of pharmaceutical product recall information to local drug manufacturers, pharmacy business establishments and medical facilities;

c) Cooperate with facilities having pharmaceutical products with quality violations in collecting additional pharmaceutical product samples as specified in Point b Clause 1 or Point b Clause 2 Article 14 of this Circular, or direct the testing facilities to do so;

d) Organize surveillance of pharmaceutical product recall in the Departments’ jurisdictions; take actions against and penalize facilities violating pharmaceutical product recall regulations within their competence;

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e) Organize and participate in coercive pharmaceutical product recall.

Chapter V

IMPLEMENTATION CLAUSE

Article 17. Effect[7]

1. This Circular comes into force from June 20, 2018.

2. The following documents shall be annulled from the effective date of this Circular:

a) The Circular No. 09/2010/TT-BYT dated April 28, 2010 of the Minister of Health;

b) The Circular No. 04/2010/TT-BYT dated February 12, 2010 of the Minister of Health.

Article 18. Implementation

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a) Take charge and cooperate with related units in organizing propagation, dissemination and implementation of this Circular;

 b)1^6 Take charge and cooperate with the National Institute of Drug Quality Control, the Institute of Drug Quality Control of Ho Chi Minh City, the National Institute for Control of Vaccines and Biologicals in formulating plans to collect pharmaceutical product samples for quality inspections carried out at facilities in charge of production, preparation, import, export, storage, wholesaling, retail and use of pharmaceutical products nationwide, and present those plans to the Ministry of Health for consideration and approval, and allocation of budget for plan implementation within the Ministry’s competence.

Collect pharmaceutical product samples for quality inspection according to the approved plans and update the Ministry of Health’s pharmaceutical quality inspection database with information on collected pharmaceutical product/pharmaceutical starting material samples (including names of pharmaceutical products/pharmaceutical starting materials, concentration, content, dosage form, batch number, expiry date, number of certificate of registration or import license, manufacturer, importer, sample collector) and the pharmaceutical product/pharmaceutical starting material quality inspection results;

c) Provide scientific and technical information on ensuring pharmaceutical product/pharmaceutical starting material quality.

Provide the National Institute of Drug Quality Control and the Institute of Drug Quality Control Ho Chi Minh City with label templates and the quality standard of the pharmaceutical product/pharmaceutical starting material that is issued marketing authorization or import license(the updated standard if any changes occur). In the case of vaccines and biologicals, the label template and quality standard shall be sent to the National Institute for Control of Vaccines and Biologicals;

d) Organize quality inspections on pharmaceutical products/pharmaceutical starting materials manufactured, prepared, marketed and used nationwide. Direct and survey the pharmaceutical product testing system nationwide. Draw conclusions on pharmaceutical product quality, based on the test results from state-owned pharmaceutical product testing facilities’ and relevant records;

dd) Take charge or cooperate in carrying out state inspections, inspect and take action against violations against the law in pharmaceutical product quality within the Administration's competence.

e)17 Take charge and cooperate with relevant competent authorities in translating, publishing and updating WHO guidelines for pharmaceutical product destruction on the website of the Drug Administration of Vietnam for reference purpose.

2. Departments of Health have the responsibility to:

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b)1^8 Formulate plans to collect pharmaceutical product/pharmaceutical starting material samples for quality inspections carried out at facilities in charge of production, preparation, import, export, storage, wholesaling, retail and use of pharmaceutical products within provinces and cities and present those plans to the provincial People’s Committees for consideration, approval and allocation of budget for plan implementation within the Committees’ competence;

c) Update the Ministry of Health’s pharmaceutical product quality inspection database with information on collected pharmaceutical product/pharmaceutical starting material samples (including: name of pharmaceutical product/pharmaceutical starting material, concentration, content, type of preparation, batch number, expiry date, marking authorization number or import license number, manufacturer, importer, sample collector) and the pharmaceutical product/pharmaceutical starting material’s quality inspection results.

3. Responsibilities of the pharmaceutical product testing system:

a)1^9 Central pharmaceutical product testing facilities (National Institute of Drug Quality Control, Institute of Drug Quality Control of Ho Chi Minh City, National Institute for Control of Vaccines and Biologicals):

-  Analyze and test samples to identify the quality of manufactured, marketed and used pharmaceutical products/pharmaceutical starting materials; report the test results to the Ministry of Health (Drug Administration of Vietnam) and the local Department of Health;

- Research, compile and publish the list of reference materials (including those of impurities) on websites of the institutes and the Drug Administration of Vietnam for analyses and tests on manufactured, imported, marketed and used in Vietnam;

- The National Institute of Drug Quality Control and the Institute of Drug Quality Control Ho Chi Minh City have the responsibility to provide pharmaceutical product testing centers in assigned provinces with physical and electronic copies of pharmaceutical product/pharmaceutical starting material quality standards;

- The National Institute for Control of Vaccines and Biologicals, on an annual basis, review and evaluate vaccine/biological quality trends and present the evaluation to the Drug Administration of Vietnam, which will review and present it to the Ministry of Health for promulgation of guidelines for lot release testing of vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma; the scope of work shall include the following elements:

+ A lot release testing policy and policy on reduced testing or exemption from testing of vaccines and biologicals that have been assessed and issued with the Batch Release Certificate by the Stringent Regulatory Authorities.

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+ Specimen of the lot summary protocols for each type of vaccine/biological.

Update information about issuance of quality certificates for vaccines and biologicals which are seria containing antibodies and derivatives of human blood and plasma on websites of the institutes and the Drug Administration of Vietnam.

b) Provincial testing facilities:

- Analyze and test samples to identify the quality of manufactured, circulated and used pharmaceutical products/pharmaceutical starting materials;

- Report the test results to the Department of Health and the Ministry of Health (Drug Administration of Vietnam).

4. Traders have the responsibility to:

a) Organize researches and carry out implementation of the regulations of law on pharmaceutical product/pharmaceutical starting material quality promulgated by this Circular;

b) Implement regulations on inspection, control of pharmaceutical products/pharmaceutical starting materials’ source and quality. Carry out quality control in order to ensure pharmaceutical product/pharmaceutical starting material quality throughout the facility's operation;

c) Establish a system of records and documents in order to monitor circulation of pharmaceutical products/pharmaceutical starting materials. Carry out monitoring and surveillance of the quality of pharmaceutical products/pharmaceutical starting materials produced by the facility; promptly discover and handle violating pharmaceutical products, report those pharmaceutical products to the pharmaceutical regulatory agencies and pharmaceutical product quality inspection authorities.

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a) The National Institute of Drug Quality Control, the Institute of Drug Quality Control Ho Chi Minh City, the National Institute for Control of Vaccines and Biologicals, by their functions, tasks and jurisdictions, to:

- Formulate plans to collect drug samples for testing and surveillance of pharmaceutical product/pharmaceutical starting material quality; reserve, receive and use the annual budget for sample collection and tests on pharmaceutical product/pharmaceutical starting material samples;

- Collect pharmaceutical product/pharmaceutical starting material samples in accordance with the approved plans at establishments doing pharmacy business and using pharmaceutical products;

- Update the Ministry of Health’s pharmaceutical product quality inspection database with information on pharmaceutical product/pharmaceutical starting material samples collected for quality inspection and those samples’ test results;

- Report the test results to the Ministry of Health (Drug Administration of Vietnam) and the local Department of Health if the pharmaceutical product/pharmaceutical starting material samples do not meet the quality standards as specified in Clause 3 Article 7 of this Circular.

- The National Institute of Drug Quality Control shall the pharmaceutical product quality inspection database for the Ministry of Health;

- [8] Recover sampling fees returned by trading establishments and costs of substandard pharmaceutical product/pharmaceutical starting material sample testing in accordance with laws.

b) Provincial testing facilities:

- Formulate plans to collect pharmaceutical product samples for testing and surveillance of pharmaceutical product/pharmaceutical starting material quality; reserve, receive and use the annual budget for sample collection and tests on pharmaceutical product/pharmaceutical starting material samples;

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- Update the Ministry of Health’s pharmaceutical product quality inspection database with information on pharmaceutical product/pharmaceutical starting material samples collected for quality inspection and those samples’ test results;

- Report the test results to the Ministry of Health (Drug Administration of Vietnam) and the Department of Health if the pharmaceutical product/pharmaceutical starting material samples do not meet the quality standards as specified in Clause 3 Article 7 of this Circular.

- [9] Recover sampling fees returned by trading establishments and costs of substandard pharmaceutical product/pharmaceutical starting material sample testing in accordance with laws.

Article 19. Responsibility for implementation

The Director General of the Drug Administration of Vietnam, Chief of the Ministry Office, Chief Inspector of the Ministry, heads of units affiliated to the Ministry of Health, provincial Departments of Health, pharmacy business establishments, other related authorities, organizations and individuals are responsible for the implementation of this Circular.

Difficulties that arise during the implementation of this Circular should be reported to the Ministry of Health for consideration and resolution./.

CERTIFIED BY

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[1] This Clause is amended by Clause 2 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[2] This Clause is amended by Clause 4 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[3] This Clause is amended by Clause 5 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[4] This Point is amended by Clause 7 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[5] This Clause is added by Clause 10 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[6] This Clause is amended by Clause 13 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[7] Article 2 of the Circular No. 03/2020/TT-BYT dated January 22, 2020 stipulates that:

“Article 2. Effect

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Article 3. Responsibility for implementation

The Director General of the Drug Administration of Vietnam, Chief of the Ministry Office, Chief Inspector of the Ministry, heads of units affiliated to the Ministry of Health, provincial Departments of Health, pharmacy business establishments, other related authorities, organizations and individuals are responsible for the implementation of this Circular.

Difficulties that arise during the implementation of this Circular should be reported to the Ministry of Health for consideration and resolution./.”

[8] This Point is added by Clause 17 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.

[9] This Point is added by Clause 18 Article 1 of the Circular No. 03/2020/TT-BYT, which comes into force from March 16, 2020.