Circular No. 12/2022/TT-BYT amends and supplements some Articles of Circular No. 35/2018/TT-BYT dated November 22, 2018, issued by the Minister of Health on Good Manufacturing Practices for the production of medicines and active pharmaceutical ingredients.

CIRCULAR

AMENDMENTS AND SUPPLEMENTS TO SOME ARTICLES OF CIRCULAR NO. 35/2018/TT-BYT DATED NOVEMBER 22, 2018 OF THE MINISTER OF HEALTH ON GOOD MANUFACTURING PRACTICES FOR MEDICINES AND ACTIVE PHARMACEUTICAL INGREDIENTS

Pursuant to the Drug Law No. 105/2016/QH13 dated April 6, 2016;

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

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

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

At the proposal of the Director of the Department of Medicine Management, the Director of the Department of Traditional Medicine and Pharmaceutical Management;

The Minister of Health issues this Circular to amend and supplement some articles of Circular No. 35/2018/TT-BYT dated November 22, 2018 of the Minister of Health on Good Manufacturing Practices for Medicines and Active Pharmaceutical Ingredients.

Article 1. Amend and supplement some articles of Circular No. 35/2018/TT-BYT dated November 22, 2018 of the Minister of Health on Good Manufacturing Practices for Medicines and Active Pharmaceutical Ingredients

1. Add Clause 13 of Article 2 as follows:

"13. Equivalent EU-GMP means the Good Manufacturing Practice principles and standards issued by the drug regulatory authorities of the SRA countries."

2. Amending and supplementing Clause 4 of Article 3 as follows:

"4. Updated GMP Principles and Standards Documents:

a) In case the World Health Organization amends or supplements the Good Manufacturing Practice principles and standards for medicines and active pharmaceutical ingredients (hereinafter referred to as updated documents) as stipulated in point a and point b of Clause 1 of this Article, within three months from the date these updated documents are published on the World Health Organization's website, the Department of Drug Management or the Department of Traditional Medicine and Traditional Medicine Management, depending on the assigned state management sector, shall organize the translation and publish the amended and supplemented contents on the Ministry of Health's website and the Department of Drug Management's website for relevant parties to search, update, and apply;

b) In case the Pharmaceutical Inspection Co-operation Scheme (PIC/S) or the European Union has updated documents as stipulated in point c and point d of Clause 1 of this Article, which have not been posted on the Ministry of Health's website and the Department of Drug Management's website, the medicine manufacturing facilities and active pharmaceutical ingredient manufacturing facilities shall be responsible for translating and confirming the translation according to the legal provisions on notarization and certification, and send it to the Department of Drug Management. Within ten days from the date of receipt of the notarized and certified translation sent by the medicine manufacturing facilities and active pharmaceutical ingredient manufacturing facilities, the Department of Drug Management shall review, revise, and post it on the Ministry of Health's website and the Department of Drug Management's website."

3. Amend and supplement Clause 3 of Article 4 as follows:

"3. Medicine manufacturing facilities and active pharmaceutical ingredient manufacturing facilities from medicinal herbs and herbal raw materials shall implement the Good Manufacturing Practice principles and standards as stipulated in Appendix V attached to this Circular."

4. Amend and supplement Clause 4 of Article 4 as follows:

"4. Traditional medicine manufacturing facilities that only produce traditional medicine formulations such as decoctions, single herbs, pills, powders, medicinal alcohol, and medicinal spirits shall implement the Good Manufacturing Practice principles and standards as stipulated in Part I of Appendix VI attached to this Circular."

5. Amend and supplement Clause 9 of Article 4 as follows:

"9. Traditional medicine manufacturing facilities and traditional medicine ingredient manufacturing facilities are permitted to implement the Good Manufacturing Practice principles and standards as stipulated in Part II of Appendix VI or Appendix I or Appendix III or Appendix IV or Appendix V attached to this Circular and the updated documents as stipulated in Clause 4 of Article 3 of this Circular."

6. Amend and supplement Clause 10 of Article 4 as follows:

"10. Antibiotics of the beta-lactam group (Penicillins, Cephalosporins, Penems, and similar), cytotoxic drugs, hormonal contraceptives, vaccines, biological products, and specific drugs with special production requirements as stipulated in the Good Manufacturing Practice principles and standards (WHO-GMP, PIC/S-GMP, EU-GMP, and equivalent EU-GMP), in addition to being produced at facilities implementing the corresponding Good Manufacturing Practice principles and standards as stipulated in this Article, must also be produced in separate production facilities and equipment with measures to prevent contamination and environmental pollution, and ensure they do not affect other products manufactured in the same area.

For anti-cancer drugs, hormonal drugs, and potent drugs not included in the aforementioned list, the determination of the necessity and degree of separation regarding facilities (facilities) and/or production equipment is based on risk assessment and guidance from the European Medicines Agency (EMA) or the World Health Organization."

7. Amend and supplement Clause 11 of Article 4 as follows:

"11. Medicine manufacturing facilities producing soft capsule formulations, oral liquid formulations, and topical formulations (creams, gels, ointments, and external liquids) using herbal extracts, decoctions, herbal powders, and essential oils that have been standardized can produce herbal medicines on the corresponding production lines and must implement the Good Manufacturing Practice principles and standards as stipulated in Appendix I or Appendix III or Appendix IV attached to this Circular and the updated documents as stipulated in Clause 4 of Article 3 of this Circular."

8. Amend Clause 1 of Article 7 as follows:

"1. Documentation used for evaluating compliance with Good Manufacturing Practice principles and standards: Documentation of WHO-GMP principles and standards or documentation of Good Manufacturing Practice principles and standards as stipulated in Clauses 2, 3, 4, 5, and 6 of Article 4 of this Circular, corresponding to the production activities of the manufacturing facility."

9. Amend Clause 6 of Article 9 as follows:

"6. After submitting the activity report and maintenance of compliance with Good Manufacturing Practice principles and standards within the prescribed time, the manufacturing facility may continue to operate in accordance with the provisions of the Medicine Law and related guiding documents until the periodic evaluation of compliance with Good Manufacturing Practice principles and standards is completed and must maintain compliance with Good Manufacturing Practice principles and standards."

10. Amend Clause 7 of Article 9 as follows:

"7. The procedures for evaluation, evaluation processes, and classification of evaluation results for compliance with Good Manufacturing Practice principles and standards shall be carried out in accordance with the provisions of Articles 6 and 7 of this Circular.

In case of natural disasters, epidemics, or wars where the receiving authority cannot carry out the evaluation of maintaining compliance with Good Manufacturing Practice principles and standards as stipulated, the receiving authority shall confirm the status of maintaining compliance with Good Manufacturing Practice principles and standards for the manufacturing facility. After overcoming the natural disaster, epidemic, or war situation, the receiving authority shall conduct the evaluation of maintaining compliance with Good Manufacturing Practice principles and standards as stipulated in Articles 6 and 7 of this Circular."

11. Amend Point h of Clause 2 of Article 11 as follows:

"h) A supplementary production facility that applies principles and standards of GMP, evaluated and certified by the drug regulatory authority SRA to meet EU-GMP or equivalent standards, and proposes the publication of its compliance."

12. Amend Clause 4 of Article 11 as follows:

“In cases where a production facility undergoes changes as stipulated in Points b, c, or d of Clause 2 of this Article, or in cases where a production facility producing sterile medicinal products or sterile raw materials for medicinal products undergoes changes as stipulated in Points đ, e, and g of Clause 2 of this Article, the production facility must submit a change report along with corresponding technical documentation to the Receiving Authority.”

a) The Receiving Authority conducts an on-site evaluation at the production facility. If the production facility meets the requirements, the Receiving Authority issues a written agreement with the changes made by the production facility;

b) The procedures for evaluating, classifying results, and handling evaluation outcomes for production facilities undergoing changes as stipulated in Point b of Clause 2 of this Article shall be carried out according to the provisions of Articles 6, 7, and 10 of this Circular;

c) The procedures for evaluating, classifying results, and handling evaluation outcomes for production facilities undergoing changes as stipulated in Points c or d of Clause 2 of this Article, or for production facilities producing sterile medicinal products or sterile raw materials for medicinal products undergoing changes as stipulated in Points đ, e, and g of Clause 2 of this Article shall be carried out according to the provisions of Articles 6, 7, and 8 of this Circular.”

13. Amend Clause 7 of Article 11 as follows:

“7. In cases where a production facility for medicinal products or raw materials for medicinal products undergoes changes as stipulated in Points đ, e, or g of Clause 2 of this Article (excluding the cases stipulated in Clause 4 of this Article), the production facility must submit a change report along with corresponding technical documentation to the Receiving Authority. The production facility must continue to ensure the maintenance of activities in accordance with GMP principles and standards.

The Receiving Authority will conduct an urgent evaluation and handle the evaluation outcomes according to the provisions of Article 12 of this Circular in cases where the change report does not adequately prove the continued compliance with GMP principles and standards at the production facility.”

14. Amend Clause 3 of Article 14 as follows:

“3. Within ten working days from the date of receiving the evaluation result indicating that the production facility complies with GMP principles and standards, based on the documents in the application file for GMP compliance evaluation, information retrieved from the database of the European Medicines Agency (EMA) and websites of drug regulatory authorities of various countries, the Receiving Authority updates the evaluation result of GMP compliance and publishes it on the Ministry of Health’s electronic portal and the electronic portal of the Receiving Authority with the following information:

a) Name and address of the production facility;

b) GMP principles and standards met (WHO-GMP, PIC/S-GMP, EU-GMP or equivalent EU-GMP), validity period of GMP compliance, name of the competent authority responsible for evaluation and certification in cases stipulated in Clauses 1 and 2 of Article 96 of Decree 54/2017/NĐ-CP, or the date of GMP compliance evaluation by the Ministry of Health of Vietnam, applicable GMP principles and standards, validity period of the GMP compliance evaluation result in cases stipulated in Point 3 of Clause 3 of Article 96 of Decree 54/2017/NĐ-CP;

c) Scope of operations of the evaluated production facility.”

15. Add Clause 4 to Article 14 as follows:

“4. Regarding the determination of the validity of GMP compliance mentioned in Point e of Clause 6 of Article 13 and Point b of Clause 3 of Article 14 during the COVID-19 pandemic or in case of natural disasters, epidemics, or war:

a) For GMP certificates issued by drug regulatory authorities of countries within the European Economic Area (EEA):

- In cases where the GMP certificate of a production facility is extended in accordance with the EMA announcement regarding the policy applied during the COVID-19 pandemic or in case of natural disasters, epidemics, or war: the validity of GMP compliance shall be implemented according to the EMA announcement;

- In cases where a new GMP certificate has been issued to the production facility, the validity of the GMP certificate shall be confirmed according to the new certificate;

b) For GMP certificates issued by authorities other than those specified in Point a of this Clause: The determination of the validity of the GMP certificate during the COVID-19 pandemic or in case of natural disasters, epidemics, or war shall be carried out according to the announcements of the drug regulatory authorities of the respective countries that have issued the GMP certificate or according to the validity period stated on the GMP certificate.”

16. Add Clause 5 to Article 19 as follows:

“5. Production facilities that have been granted GMP certificates with a scope of manufacturing traditional herbal medicines still valid before the effective date of this Circular may continue to produce traditional medicines.”

17. Amend Section 4.1.14 in Model 05 of Appendix X as follows:

“4.1.14. Traditional herbal medicine.”

18. Add Section 4.1.15 in Model 05 of Appendix X as follows:

“4.1.15. Other.”

Article 2. Abolish certain phrases, points, and clauses of Circular No. 35/2018/TT-BYT dated November 22, 2018, issued by the Minister of Health on Good Manufacturing Practices for Medicines and Active Pharmaceutical Ingredients.

1. Abolish point b of Clause 5 of Article 11.

2. Abolish Clause 6 of Article 11.

3. Remove the phrase “or PIC/S - GMP or EU - GMP” from Form 01 of Appendix X.

4. Remove the phrase “or Pharmaceutical Inspection Cooperation Scheme (PIC/S) or European Union (EU)” from Form 05 of Appendix X.

Article 3. Effectiveness

This Circular takes effect from January 5, 2023.

Article 4. Responsibilities for Implementation

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

In the course of implementation, if there are difficulties or obstacles, please report them to the Ministry of Health (Drug Administration Department, Traditional Medicine Department) for consideration and resolution./.