Chương I Thông tư 32/2018/TT-BYT: Quy định chung

Chapter I

GENERAL PROVISIONS

Article 1. Scope

1. This Circular provides for:

a) Documents procedures for issuance, renewal, revision and revocation of the marketing authorization (also called licensing, registration, approval, etc.) of modern medicines, vaccines, biologicals, herbal ingredients and medicinal ingredients (active ingredients, semi-finished herbal ingredients, excipients, capsule shells) for human use in Vietnam;

b) Required clinical data for assurance of safety and efficacy in the application;

c) Requirements for exemption from clinical trial or certain stages thereof in Vietnam; drugs that have to undergo Stage 4 clinical trial;

d) Rules for validating applications for the marketing authorization of drug/medicinal ingredient (hereinafter referred to as “marketing application”), renewal and revision thereof;

dd) Rules for validating applications for the license to import drugs that are yet to be approved for marketing authorization (hereinafter referred to as “unapproved drugs”) in the cases specified in Point a Clause 43 Article 5 of Decree No. 155/2018/ND-CP;

e) Rules for organization and operation of Marketing Authorization Advisory Board (hereinafter referred to as “the Advisory Board”);

g) Procedures for validating marketing applications, renewal and revision thereof; application for the license to import unapproved drugs.

2. This Circular does not apply to the cases mentioned in Clause 2 Article 54 of the Law on Pharmacy, which provides for medicinal ingredients that are not required to be registered before marketing authorization in Vietnam, and semi-finished herbal ingredients produced by the same producer of the drug products.

Article 2. Definitions

For the purpose of this Circular, the terms below are construed as follows:

1. ASEAN common technical dossier (ACTD) means the document providing guidelines for registration of drugs that satisfy ASEAN Common Technical Requirements (ACTR), which are specified in Appendix I hereof.

2. ICH-CTD means the common technical document provided by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use.

3. “major variations” are variations that clearly and directly affect the quality, safety and efficacy of the drug, specified in Appendix II hereof.

4. “”minor variations” are variations that do not affect or barely affect the quality, safety and efficacy of the drug, specified in Appendix II hereof.

5. “applicant” or “authorization holder” means the establishment that applies for the marketing authorization, renewal or revision thereof.

6. “manufacturer” means the establishment that carry out one or some or all of the manufacturing processes or release of the batch of drug.

7. “ingredient manufacturer” means the establishment that manufactures or releases the ingredient(s) of the drug product.

8. “product license holder” or “product owner” of a foreign drug means the establishment responsible for the drug product and is written on the Certificate of pharmaceutical product (CPP).

9. “reference authorities” mentioned in this Circular include: European Medicines Agency (EMA), drug regulatory authorities of the USA, Japan, France, Germany, Sweden, England, Switzerland, Australia, Canada, Belgium, Austria, Ireland, Denmark and Netherland

10. Stringent Regulatory Authorities (SRA) area drug regulatory authorities that are considered SRA by WHO. A SRA is:

a) a member of ICH before October 23, 2015, including: US-FDA, drug regulatory authorities of European Commission, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), and Japan’s Pharmaceuticals Medical Devices Agency (PMDA);

b) an ICH observers before October 23, 2015, including: European Free Trade Association (EFTA), Swissmedic and Health Canada;

c) a regulatory authority associated with an ICH member through a legally-binding, mutual recognition agreement before October 23, 2015, including: Australia, Iceland, Liechtenstein and Norway.

11. “Certificate of pharmaceutical product (CPP)” means a certificate issued in the format recommended by WHO according to WHO’s Certification Scheme on the Quality of Pharmaceutical Products Moving in International Commerce.

12. “semi-finished herbal ingredients” are medicinal ingredients derived from herbs in the form of glue, granule, powder, extract, essential oil, resin, gum, jelly.

Article 3. Responsibilities of applicants/authorization holders

1. Take responsibility for any revision to the label or package insert; comply with update request of the Ministry of Health (Drug Administration of Vietnam) during the effective period of the marketing authorization without having to submit an application for revision.

2. Apply for revision according to Clause 4 Article 28 and Article 40 of this Circular during effective period of the marketing authorization.

3. Ensure quality, safety and efficacy of the drugs/medicinal ingredients as declared in the application.

4. Take responsibility for legitimacy and accuracy of every document in the application. Cooperate with the foreign authority and manufacturer in responding to inquiries of Drug administration of Vietnam regarding the authenticity of legal documents in the application.

5. Send a written notice to Drug Administration of Vietnam within 30 days from the day on which the marketing authorization is revoked in any country if the drugs/medicinal ingredients have been granted the marketing authorization in Vietnam, and specify the reason for such revocation.

6. At the request of a competent authority, cooperate with the manufacturer in ensuring that at least one of the two studies or provides additional information about the to-be-marketed drug when there is information or evidence about the safety and efficacy of the drug during the effective period of its market authorization.

7. Cooperate with the manufacturer, importer and distributor in monitoring, collecting and analyzing information, and send a report to Drug Information and Adverse Reaction Center (DI&ADR) on post-vaccination reactions and adverse reaction of the drug in accordance with Clause 5 Article 77 of the Law on Pharmacy, guidelines for Good Pharmacovigilance Practices, national guidelines for pharmacovigilance and relevant regulations.

8. Maintain the marketing authorization holder’s eligibility for operation during the effective period of the marketing authorization. In cases where the current authorization holder is no longer eligible for operation, it shall follow procedures for changing the authorization holder in accordance with Clause 4 Article 28 and Article 40 of this Circular within 30 days from the day on which the marketing authorization holder no longer qualifies for operation.

9. Take responsibility for issues relevant to intellectual property rights of the drugs/medicinal ingredients registered in Vietnam.

10. Cooperate with the manufacturer in updating specifications of drugs/medicinal ingredients in accordance with Circular No. 11/2018/TT-BYT and Circular No. 13/2018/TT-BYT.

11. Implement the approved risk management plan in the application for issuance or renewal of the marketing authorization for vaccines.

12. Take responsibility in accordance with Clause 2 Article 57 of the Law on Pharmacy and provisions of this Article for the proposed drugs/medicinal ingredients from the day on which Drug Administration of Vietnam signs the permission for changing the marketing authorization holder, including the drugs/medicinal ingredients approved for marketing authorization before such permission is signed.

13. Assume other responsibility specified in this Circular and relevant regulations of law.

Article 4. Responsibilities of manufacturers of drugs/medicinal ingredients

1. Manufacture the drugs/medicinal ingredients at the factory having the manufacture license issued by a competent authority.

2. Request revocation of the marketing authorization in case the drug/medicinal ingredient may affect users’ health in terms of their quality, safety or efficacy (Form No. 1/TT enclosed herewith)

3. Cooperate with the applicant/authorization holder in implementation of Clause 1, 2, 3 Article 3 of this Circular.

4. Cooperate with the applicant/authorization holder in fulfilling competent authorities’ request for inspection or evaluation of the manufacturing facility.

5. Maintain the operating conditions of the manufacturing facility throughout the effective period of the marketing authorization.

6. Follow procedures for changing the authorization holder within 30 days from the day on which Drug Administration of Vietnam signs the notice that the current authorization holder is no longer qualified for operation.

7. Update specifications of drugs/medicinal ingredients in accordance with Circular No. 11/2018/TT-BYT.

Article 5. Reporting monitoring and evaluation of safety and efficacy

1. Pharmaceutical-trading establishments and health facilities shall monitor, collect information, and submit reports to competent authorities on post-vaccination reactions and adverse reaction of the drug in accordance with Article 77 and Article 78 of the Law on Pharmacy, guidelines for Good Pharmacovigilance Practices, national guidelines for pharmacovigilance and relevant regulations.

2. The authorization holders shall submit reports on safety and efficacy of the drugs specified in Clause 2 Article 8 of this Circular (Form No. 2A/TT for drugs or 2B/TT for vaccines):

a) to DI&ADR every 6 months throughout the effective period of the marketing authorization.

b) when applying for renewal of the marketing authorization at Drug Administration of Vietnam.

3. Health facilities using the drugs specified in Clause 2 Article 8 of this Circular shall submit the report on the use of drugs (Form No. 2C/TT) to DI&ADR every 6 months throughout the effective period of the marketing authorization.

Article 6. Language, format, quantity of documents

1. Language of documents in the marketing application

Every document in the marketing application shall be written in Vietnamese or English language. The package insert and summary shall be written in Vietnamese language.

2. Documents in the marketing application shall be A4 papers and firmly bound (except online applications). The application shall have covers (Form No. 3/TT), product information sheet (Form No. 4/TT) and arranged in the order specified in the Table of Contents (Form No. 5/TT). Different sections are separated from each other. The sections shall be numbered and bear the applicant’s or manufacturer’s seal on the first page (for foreign drug, the seal of the representative office is acceptable).

The following documents shall be bound separately and enclosed with 01 product information sheet:

a) Bioequivalence study documents;

b) Non-clinical and clinical documents;

c) Documents serving GMP evaluation according to Article 95 and Article 98 of the Government's Decree No. 54/2017/ND-CP dated May 08, 2017 on elaboration of the Law on Pharmacy.

3. Different drugs (except vaccines) may be included in the same application if the following elements are the same: Drug name, dosage form, route of administration, specifications; manufacturer’s name and address, formula, content active ingredient per unit dose (for metered-dose solid drugs), content or concentration of active ingredient (for non-metered solid drugs, liquid drugs or semi-solid drugs; concentration or content of active ingredient and material of the primary package (for parenteral drugs).

4. Quantity of mandatory documents in the application for issuance or renewal of the marketing authorization:

a) For modern drugs, vaccines, biologicals: 01 set of documents specified in Clauses 1, 2, 3, 5, 6, 7 Article 28 of this Circular; For herbal ingredients and medicinal ingredients: the documents specified in Clause 1 and Clause 2 Article 31, Clause 1 and Clause 2 Article 33 of this Circular;

b) For vaccines: 01 copy of every document; For other cases: 02 copies of the following documents: application form, specifications, test method;

c) 02 set of samples of the label of the drug/medicinal ingredient and the package insert bearing the seal of the applicant (or seal of the representative office for foreign drugs) or manufacturer. The labels shall be attached to or presented on A4 papers.

5. Quantity of mandatory documents in the application for revision of the marketing authorization:

a) For modern drugs, vaccines, biologicals and the cases mentioned in Clause 3 Article 31: 01 set of documents specified in Clause 4 Article 28 of this Circular; For herbal ingredients and medicinal ingredients: the documents specified in Clause 1 Article 31 and Clause 3 Article 33 of this Circular.

b) For revision to the label or package insert: 02 sets of samples of the label and the package insert bearing the seal of the applicant (or seal of the representative office for foreign drugs) or manufacturer. The labels shall be attached to or presented on A4 papers.

6. Online application:

a) 01 set of documents specified in this Circular shall be submitted online and 01 set of physical documents (except labels and package inserts) shall be sent to Drug Administration of Vietnam;

b) The online application roadmap shall be announced by the Ministry of Health.

Article 7. Marketing authorization fees

Applicants shall pay the fees for issuance of the marketing authorization in accordance with applicable regulations of law on fees and charges.

Article 8. Effective periods, symbols of the marketing authorization and deadline for renewal

1. The effective period of a marketing authorization is 05 years from the issuance date or renewal date, except for the case specified in Clause 2 of this Article.

2. The effective period of the marketing authorization for the following drugs is 03 years:

a) New drugs and vaccines that apply for the marketing authorization for the first time, reference biologicals and similar biologicals that apply for the marketing authorization in Vietnam for the first time;

b) Drugs having the same active ingredient(s), concentration, content or dosage form as that of the new drug which has not been granted a 5-year marketing authorization;

c) Any drug other than those mentioned in Point a and Point b of this Clause if a report on their safety and efficacy is not submitted when applying for renewal of the marketing authorization because the drug has not been marketed in reality or the quantity of drug used, quantity of patients or use duration is insufficient according to the Advisory Board, or the health facility recommends extension of monitoring of the safety and efficacy of the drug;

d) The cases in which the monitoring of safety and efficacy of the drug should be continued as recommended by the Advisory Board.

3. Within 12 months before the expiration date of the marketing authorization, its holder may apply for renewal. The marketing authorization cannot be renewed after it expires, in which case an application for issuance of a new marketing authorization shall be submitted.

4. Each marketing authorization has a separate number, which helps recognize domestically manufactured and import drugs, medicinal ingredients, vaccines, biologicals, drugs under technology transfer agreements, drugs undergoing secondary packaging in Vietnam.

5. If a new marketing authorization is granted during the effective period of the old marketing authorization, both of them can be simultaneously effective and the latter will be effective for 06 months from the effective date of the former.

Article 9. Criteria for recognition of proprietary drugs

1. The drug proposed as proprietary drug (except biologicals) shall be specified in the marketing application and satisfy all of the following criteria:

a) The safety and efficacy data is sufficient as prescribed in Article 13 of this Circular;

b) The drug is approved for marketing authorization by one of the regulatory authorities mentioned in Clause 9 and Clause 10 Article 2 of this Circular, except for new drugs that are manufactured in Vietnam.

In case of change of manufacturer or technology transfer of the proprietary drug in Vietnam according to Clause 2 or Clause 3 of this Article, it will be still recognized as a proprietary drug.

2. In cases where a proprietary drug is declared by the Ministry of Health as prescribed in Clause 1 of this Article and one, some or all of its manufacturing processes is transferred to a manufacturer in Vietnam, the proprietary drug and the drugs manufactured in Vietnam must satisfy all of the following criteria:

a) The formulae are the same;

b) The manufacturing processes are the same;

c) The material quality specifications are the same;

d) The drug product specifications are the same;

dd) In case of any changes to the criteria mentioned in Point a, b, c or d of this Clause, the applicant shall provide data proving that the quality of the drugs manufactured in Vietnam is equivalent to that of the proprietary drug before carrying out the transfer.

3. In case of change of the manufacturer of a recognized proprietary drug, the drug granted the new marketing authorization of the new manufacturer will also be recognized as a proprietary drug if the applicant makes a written request and all of the following criteria are satisfied:

a) The drug is approved for market authorization by one of the regulatory authorities mentioned in Clause 9 and Clause 10 Article 2 of this Circular;

b) The drugs satisfy all of the criteria specified in Point a through d Clause 2 of this Article.

Article 10. Requirements for marketing authorization of domestically manufactured drugs under technology transfer agreements and drug undergoing secondary packaging in Vietnam

1. Requirements for marketing authorization of drugs under technology transfer agreements:

a) The technology transfer may involve one, some or all of the manufacturing processes of the drug product. This does not include secondary packaging transfer;

b) The to-be-marketed drug and the original drug shall satisfy all of the following criteria:

- The formulae are the same;

- The manufacturing processes are the same;

- The material quality specifications are the same;

- The drug product specifications are the same;

In case of any changes to the aforementioned requirements, the applicant shall provide data proving that the quality of the drugs manufactured in Vietnam is equivalent to that of the original drug.

c) Regarding generic drugs with systemic action, the original drug must have demonstrated bioequivalence, unless the drug has a dosage form that is exempt from bioequivalence testing according to Circular No. 08/2010/TT-BYT.

d) The documents satisfy the requirements specified in Clause 5 Article 28 of this Circular.

2. Drugs undergoing secondary packaging in Vietnam

a) Within 05 years from the issuance date of the marketing authorization, the authorization holder and the manufacturer shall complete the technology transfer under the conditions specified in Clause 1 of this Article. Within 03 years from the issuance date of the marketing authorization, the authorization holder shall submit a report on the technology transfer progress (Form No. 6/TT enclosed herewith);

b) The documents satisfy the requirements specified in Clause 6 Article 28 of this Circular.

3. The drug before technology transfer and secondary packaging may be marketed until expiration of the marketing authorization.

Article 11. Confidentiality of information in the marketing application dossier

The applicant that wishes to keep the information in the marketing application dossier confidential shall follow instructions in Circular No. 05/2010/TT-BYT and specify the request in Form No. 6/TT enclosed herewith.

Article 12. Verification of information on legal documents

1. Drug Administration of Vietnam shall cooperate with diplomatic agencies and relevant domestic and overseas authorities in verifying the authenticity of legal documents in marketing application dossiers. Such legal documents include:

a) The CPP of every application for issuance, renewal or revision of the marketing authorization;

b) For foreign applicants that apply for marketing authorization in Vietnam for the first time: legal documents issued by overseas competent authorities.

2. The verification shall be simultaneous with validation of the marketing application dossier and within the time limit specified in Clause 5 Article 56 of the Law on Pharmacy