| MINISTRY OF HEALTH OF VIETNAM | SOCIALIST REPUBLIC OF VIETNAM |
| No. 04/VBHN-BYT | Hanoi, April 11, 2023 |
CIRCULAR
GOOD MANUFACTURING PRACTICES FOR PHARMACEUTICAL PRODUCTS AND PHARMACEUTICAL STARTING MATERIALS
Circular No. 35/2018/TT-BYT dated November 22, 2018 of the Minister of Health of Vietnam on Goods Manufacturing Practices for pharmaceutical products and pharmaceutical starting materials, effective as of January 10, 2019, is amended by:
Circular No. 29/2020/TT-BYT dated December 31, 2020 of the Minister of Health of Vietnam on amendments to and annulment of some legislative documents promulgated or jointly promulgated by the Minister of Health of Vietnam, effective as of February 15, 2021.
Circular No. 12/2022/TT-BYT dated November 21, 2022 of the Minister of Health of Vietnam on amendments to Circular No. 35/2018/TT-BYT dated November 22, 2018 of the Minister of Health of Vietnam prescribing good manufacturing practices for pharmaceutical products and pharmaceutical starting materials, effective as of January 5, 2023.
Pursuant to Law No. 105/2016/QH13 on Pharmacy dated April 6, 2016;
Pursuant to Decree No. 54/2017/ND-CP dated May 8, 2017 of the Government of Vietnam elaborating on the Law on Pharmacy;
Pursuant to Decree No. 155/2018/ND-CP dated November 12, 2018 of the Government of Vietnam on amendments to regulations related to business conditions under state management of the Ministry of Health of Vietnam;
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At the request of the Director of the Drug Administration of Vietnam and the Director of the Traditional Medicine Administration of Vietnam,
The Minister of Health of Vietnam hereby promulgates a Circular on Goods Manufacturing Practices for pharmaceutical products and pharmaceutical starting materials. Please sign up or sign in to your TVPL Pro Membership to see English documents.
3. “Deficiency” means a deviation from GMP principles or other applicable regulations on pharmacy management.
4. “GMP” stands for Good Manufacturing Practices.
5. “WHO” stands for World Health Organization.
6. “WHO - GMP” means Good Manufacturing Practices of World Health Organization.
7. “PIC/S” stands for Pharmaceutical Inspection Co-operation Scheme.
8. “PIC/S - GMP” means Good Manufacturing Practices of Pharmaceutical Inspection Co-operation Scheme.
9. “EU” stands for European Union.
10. “EU - GMP” means Good Manufacturing Practices of European Union.
11. “US” stands for United States.
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2. The following GMP principles shall be promulgated:
a) Principles of GMP for herbal pharmaceutical products provided in the Appendix V hereof;
b) Principles of GMP for traditional pharmaceutical products provided in the Appendix VI hereof;
c) Principles of GMP for prepared traditional medicinal materials provided in the Appendix VII hereof.
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a) If WHO makes any revision to GMP principles (hereinafter referred to as “updated documents”) specified in Points a and b clause 1 of this Article, within 3 months from the date on which updated documents are published on WHO’s web portal; the Drug Administration of Vietnam or the Traditional Medicine Administration of Vietnam shall, within its jurisdiction, translate and publish the revisions on the web portal of the Ministry of Health of Vietnam and the website of the Drug Administration of Vietnam or Traditional Medicine Administration of Vietnam for retrieval, updating and application by relevant entities;
b) If the Pharmaceutical Inspection Co-operation System (PIC/S) or the European Union has the updated documents specified in points c and d clause 1 of this Article, which have not been published on the web portal of the Ministry of Health of Vietnam and the website of the Drug Administration of Vietnam, manufacturers of pharmaceutical products and pharmaceutical starting materials applying such documents shall do the translation, certify translations in accordance with regulations of law on notarization and authentication and send them to the Drug Administration of Vietnam. Within 10 days from the date on which notarized and certified true translations are received, the Drug Administration of Vietnam shall consider, correct and publish them on the web portal of the Ministry of Health of Vietnam and the website of the Drug Administration of Vietnam.
Article 4. Application of GMP principles
1. Manufacturers of pharmaceutical products and pharmaceutical starting materials shall apply GMP principles specified in the Appendix I or Appendix III or Appendix IV hereof and updated documents specified in Clause 4 Article 3 hereof.
2. Manufacturers of biological medicinal products derived from human blood or plasma shall apply GMP principles specified in the Appendix II hereof and updated documents specified in Clause 4 Article 3 hereof.
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8. Manufacturers of herbal pharmaceutical products, traditional pharmaceutical products and prepared traditional medicinal materials shall apply GMP principles specified in the Appendix I or Appendix III or Appendix IV hereof and updated documents specified in Clause 4 Article 3 hereof.
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b) 6 months in case of updates other than those specified in Point a of this Clause, from the date on which updated documents are published on the web portal of the Ministry of Health of Vietnam and the website of the Drug Administration of Vietnam.
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3. If the manufacturer applying for certificate of eligibility for pharmacy business sells pharmaceutical products and pharmaceutical starting materials to wholesalers, retailers or health facilities, documents about its technologies and personnel according to Clause 2 Article 32 of the Decree No. 54/2017/ND-CP are required when it applies for both certificate of GDP compliance and certificate of eligibility for pharmacy business. The receiving authority shall inspect its compliance with both GDP and GMP in accordance with regulations on GDP.
Article 6. Sequence of inspection of GMP compliance
1. Receipt of applications:
The manufacturer shall submit an application, which includes the documents specified in Article 5 herein, accompanied by the application fees in accordance with regulations of the Minister of Finance of Vietnam to:
a) The Traditional Medicine Administration of Vietnam if the manufacturer applies for the certificate for eligibility for pharmacy business that allows manufacture of herbal materials, traditional pharmaceutical products and prepared traditional medicinal materials at the time of submission;
b) The Drug Administration of Vietnam if the manufacturer applies for the certificate for eligibility for pharmacy business that allows manufacture of pharmaceutical starting materials (excluding herbal materials), chemical pharmaceutical products, herbal pharmaceutical products, vaccines and biologicals;
c) The Drug Administration of Vietnam if the manufacturer applies for the certificate for eligibility for pharmacy business that allows manufacture of both one of the pharmaceutical products and pharmaceutical starting materials specified in Point a of this Clause and one of the pharmaceutical products and pharmaceutical starting materials specified in Point b of this Clause at the time of submission.
2. Procedures for receiving and processing applications:
Comply with Clause 2 and Clause 5 Article 33 of Decree No. 54/2017/ND-CP and Clause 12 Article 5 of Decree No. 155/2018/ND-CP.
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Within 15 days from the date of issuing the decision, the inspectorate shall carry out a site inspection of the manufacturer.
Article 7. Procedures for inspection and classification of GMP compliance
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e) Step 6. The inspection record is completed as follows:
The inspectorate shall make a GMP inspection report using the Form No. 04 in the Appendix X hereof, list, analyze and classify deficiencies that need to be rectified by the manufacturer, make a comparison of corresponding regulations specified in legal documents and GMP, and assess the level of GMP compliance. The deficiency classification and assessment of level of GMP compliance (applied to each production line) are prescribed in the Appendix IX hereof.
3. Level of GMP compliance:
The inspection of manufacturer's compliance with GMP specified in Appendix IX hereof shall be carried out according to the following 4 levels:
a) GMP level 1 manufacturer;
b) GMP level 2 manufacturer;
c) GMP level 3 manufacturer;
d) GMP level 4 manufacturer.
Article 8. Processing results of inspection of GMP compliance
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Within 10 working days from the date of signing the inspection record, the receiving authority shall request the Minister of Health of Vietnam to issue the certificate of eligibility for pharmacy business and issue the Certificate of GMP compliance according to Form No. 05 in the Appendix X hereof if the manufacturer applies for both certificate of GMP compliance and certificate of eligibility for pharmacy business.
2. If the GMP inspection report indicates that the manufacturer complies with GMP at level 2 as prescribed in Point b Clause 3 Article 7 of this Circular:
a) Within 5 working days from the date of signing the inspection record, the receiving authority shall send the GMP inspection report to the manufacturer as prescribed in Point b Clause 6 Article 33 of the Decree No. 54/2017/ND-CP.
b) Upon completion of deficiency rectification, the manufacturer shall submit a rectification report including a plan and evidences (such as documents, images, videos, certificates or other documentary evidences) for completion of rectification of deficiencies specified in the GMP inspection report.
c) Within 20 days from the receipt of the rectification report, the receiving authority shall assess result of deficiency rectification by the manufacturer and conclude the level of its GMP compliance. To be specific:
- If the result of deficiency rectification makes the manufacturer comply with GMP, the receiving authority shall request the Minister of Health of Vietnam to issue the certificate of eligibility for pharmacy business and the certificate of GMP compliance according to the Form No. 05 in the Appendix X hereof if the manufacturer applies for both certificate of GMP compliance and certificate of eligibility for pharmacy business;
- If the result of deficiency rectification shows that the manufacturer still fails to comply with GMP, the receiving authority shall respond and provide explanation in writing.
d) Within 6 months from the date on which additional documents are requested in writing by the receiving authority, the manufacturer shall submit them as requested. If the manufacturer fails to satisfy such request by the aforementioned deadline or the application is not satisfactory within 12 months from the first time it is submitted, the application will be rejected.
3. If the GMP inspection report indicates that the manufacturer complies with GMP at level 3 as prescribed in Point c Clause 3 Article 7 of this Circular:
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Within 20 days from the receipt of the rectification report, the receiving authority shall carry out a site inspection of deficiency rectification at the manufacturer before concluding the level of GMP compliance as prescribed in Point c Clause 2 of this Article.
4. If the GMP inspection report indicates that the manufacturer complies with GMP at level 4 as prescribed in Point d Clause 3 Article 7 of this Circular:
Within 5 working days from the date of signing the inspection record, the receiving authority shall send a notification of failure to comply with GMP enclosed with a GMP inspection report to the manufacturer and shall not issue the certificate of eligibility for pharmacy business.
5. In the cases where the manufacturer does not agree with the deficiency stated by the inspectorate, within 30 days from the date on which the inspectorate sends GMP inspection report or rectification report, the manufacturer shall submit a written recommendation enclosed with evidences (such as documents, images, videos and certificates) related to such deficiency to the receiving authority.
Within 10 working days from the receipt of the written recommendation, the receiving authority shall review GMP inspection report and written recommendation submitted by the manufacturer, if necessary, consult relevant exports and respond to the manufacturer in writing. The written response must clearly specify agreements and disagreements with the written recommendation submitted by the manufacturer and reasons for disagreements. The abovementioned length of time shall not add to the time limit for inspection.
6. Within 5 working days from the date of issuing the certificate of eligibility for pharmacy business, the receiving authority shall publish the following information on its website and web portal of the Ministry of Health of Vietnam:
a) Name and address of the manufacturer;
b) Full name of the person in charge of pharmacy, person in charge of quality assurance and number of his/her pharmacy practicing certificate;
c) Number of the certificate of eligibility for pharmacy business and Certificate of GMP compliance (if any);
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dd) Scope of operation of the manufacturer;
e) EU - GMP certificate number, validity period and issuing authority if the manufacturer has its compliance with EU - GMP or equivalent inspected by SRA.
Chapter IV
INSPECTION OF GMP COMPLIANCE AND MAINTENANCE THEREOF
Article 9. Periodic inspection of GMP compliance
1. GMP compliance by a manufacturer shall be periodically inspected every 3 years from the date of signing the previous inspection record (except surprise inspections or audits by the Ministry of Health of Vietnam or the Department of Health).
2. In November, every receiving authority shall publish the plan for periodic inspection of GMP compliance by manufacturers in the succeeding year on its website and send it to manufacturers that are mentioned in the plan. Regarding the manufacturer specified in Point c Clause 1 Article 6 of this Circular, the Drug Administration of Vietnam shall publish and implement the periodic inspection plan, except in the cases where the manufacturer applies for a particular inspection.
3. At least 30 days prior to the date of carrying out periodic inspection of GMP compliance according to the published plan, the manufacturer shall submit a report on its manufacture of pharmaceutical products and pharmaceutical starting materials and GMP compliance (hereinafter referred to as “operation and GMP compliance report”) according to the Form No. 2 in the Appendix X hereof enclosed with updated technical documents about infrastructure, technologies and personnel of the manufacturer (in case any change is made) to the receiving authority.
E.g.: If the estimated date of periodic inspection of the manufacturer A is on August 18, 2018, the manufacturer A is required to submit an operation and GMP compliance report to the receiving authority by July 18, 2018.
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5. Within 45 days from the date on which the operation and GMP compliance report is requested in writing by the receiving authority, the manufacturer shall submit the report enclosed with a written explanation for its delay in submission. By the aforementioned deadline, if the manufacturer fails to submit the report, the receiving authority shall carry out an surprise inspection or audit of GMP compliance by the manufacturer as prescribed in Article 12 of this Circular.
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c) Within 20 days from the receipt of the rectification report, the receiving authority shall assess result of deficiency rectification by the manufacturer and conclude the level of its GMP compliance. To be specific:
- If the result of deficiency rectification makes the manufacturer comply with GMP, the receiving authority shall update information about the maintenance of GMP compliance by the manufacturer on its website and web portal of the Ministry of Health of Vietnam as prescribed in Clause 6 Article 8 of this Circular and issue the Certificate of GMP compliance according to Form No. 05 in the Appendix X hereof if the manufacturer applies for the certificate of GMP compliance;
- If the result of deficiency rectification shows that the manufacturer still fails to comply with GMP, the receiving authority shall request the manufacturer in writing to take more corrective actions against deficiencies and submit an additional report. The manufacturer shall have 45 days from the receipt of the written request to complete corrective actions and send report thereof as requested.
d) Within 90 days from the date of signing the inspection record, if the manufacturer fails to submit the rectification report or still fails to comply with GMP after rectifying deficiencies, the receiving authority shall send a notification of failure to comply with GMP and impose one or some measures prescribed in Points a and b Clause 4 of this Clause depending on the nature and level of non-compliance with GMP.
3. If the GMP inspection report indicates that the manufacturer complies with GMP at level 3 as prescribed in Point c Clause 3 Article 7 of this Circular:
Processing order and time of result of inspection of GMP compliance are specified in Clause 2 of this Article.
Within 20 days from the receipt of the rectification report, the receiving authority shall carry out a site inspection and supervision of deficiency rectification at the manufacturer before concluding the level of GMP compliance as prescribed in Point c Clause 2 of this Article.
4. If the GMP inspection report indicates that the manufacturer complies with GMP at level 4 as prescribed in Point d Clause 3 Article 7 of this Circular:
Within 5 working days from the date of signing the inspection record, according to the assessment of risks of deficiencies in the quality of pharmaceutical products and pharmaceutical starting materials, and pharmaceutical product user safety, the receiving authority shall send a notification of failure to comply with GMP enclosed with a GMP inspection report. Depending on the nature and level of non-compliance with GMP, the receiving authority shall impose one or some of the following measures:
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b) Request the Minister of Health of Vietnam to issue a decision on revocation of the certificate of eligibility for pharmacy business as prescribed in Clause 2 Article 40 of the Law on Pharmacy and revoke the certificate of GMP compliance (if any).
c) If the manufacturer is ineligible for one or several business activities specified in its certificate of eligibility for pharmacy business, the receiving authority shall:
- Request the Minister of Health of Vietnam to issue a decision on revocation of the certificate of eligibility for pharmacy business to remove the business activity for which the manufacturer is ineligible and issue a new certificate of eligibility for pharmacy business which is conformable with the business activity for which the manufacturer is eligible;
- Issue the certificate of GMP compliance which is conformable with the business activity for which the manufacturer is eligible if it so wishes.
5. Within 5 working days from the date of concluding that the manufacturer maintains its compliance with GMP or issuing the decision on revocation of the issued certificate of eligibility for pharmacy business because of the manufacturer’s failure to maintain GMP compliance, the receiving authority shall update GMP compliance status on its website as prescribed in Clause 6 Article 8 of this Circular if the manufacturer complies with GMP or information about the revocation of the certificate of eligibility for pharmacy business or Certificate of GMP compliance (if any) if the manufacturer fails to maintain its GMP compliance.
6. If it is concluded that a sample of pharmaceutical product or pharmaceutical starting material collected by the inspectorate during the inspection violates quality regulations, the receiving authority shall handle it in accordance with applicable regulations.
Article 11. Control of changes
1. Before making one of the changes specified in Points a and b of this Clause, a vaccine manufacturer shall send a notification including the result of assessment of risks and effect of changes expected to be made on the product quality and safety:
a) Changes specified in Points d, dd, e and g Clause 2 of this Article;
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Within 15 days, the Drug Administration of Vietnam shall respond in writing in case it does not agree with the changes proposed by the vaccine manufacturer.
2. After making any change, the manufacturer shall apply for the certificate of eligibility for pharmacy business or submit a report on its change using the Form No. 06 in the Appendix X hereof if:
a) Making one of the changes specified in Point b Clause 1 Article 36 of the Law on Pharmacy; or
b) Changing the location of a factory at the same business location; or
c) Opening a new factory at the same business location; or
d) Expanding existing factory; or
dd) Repairing or having significant changes in structure and floor plan of the premises and production line, which results in changes to environmental conditions and manufacturing process; or
e) Changing important manufacturing equipment, thereby affecting manufacturing process and quality of pharmaceutical products and pharmaceutical starting materials; or
g) Changing auxiliary system or principle of designing and operating utility systems, thereby affecting manufacturing environment; or
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3. In case of changes specified in Point a Clause 2 of this Article, the manufacturer shall submit an application for the certificate of eligibility for pharmacy business as prescribed in Clause 2 and Clause 4 Article 38 of the Law on Pharmacy.
The order for inspecting, classifying, and processing the result of inspection of GMP compliance is specified in Articles 6, 7 and 8 of this Circular.
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