Thông tư 22/2009/TT-BYT đăng ký thuốc

CIRCULAR

ON REGISTRATION OF DRUGS

THE MINISTRY OF HEALTH

Pursuant to the Government's Decree No. 188/2007/ND-CP of December 27, 2007, defining the functions, tasks, powers and organizational structure of the Ministry of Health;

Pursuant to the June 14, 2005 Pharmacy Law;

Pursuant to the Government's Decree No. 79/ 2006/ND-CP of August 9, 2006, detailing a number of articles of the Pharmacy Law;

At the proposal of the director of the Drug Administration of Vietnam;

The Ministry of Health provides for the registration of human-use drugs for circulation in Vietnam as follows:

Chapter I

GENERAL PROVISIONS

Article 1. Scope of regulation and subjects of application

1. This Circular provides for the registration of human-use drugs for circulation in Vietnam.

2. This Circular applies to domestic and foreign agencies, organizations and individuals conducting activities related to the registration of drugs for circulation in Vietnam.

When a treaty to which the Socialist Republic of Vietnam is a contracting party contains provisions different from those of this Circular, that treaty prevails.

Article 2. Interpretation of terms

In this Circular, the terms below are construed as follows:

1. Drug means a substance or a mixture of substances for human use for disease prevention, treatment or diagnosis or adjustment of bodily physiological functions, including finished drugs, drug materials, vaccines and biologicals, except functional foods.

2. Pharmaceutical drug means a drug containing active ingredients whose composition, formula and purity have been identified.

3. Drug material means a substance constituting a drug product in the process of manufacture.

4. Drug from medicinal materials means a drug manufactured from a natural material from animals, plants or minerals.

Drugs with pure active ingredients extracted from medicinal materials and drugs with the combination of medicinal materials and synthetic chemical active ingredients are not drugs from medicinal materials.

5. Oriental medicament means a drug prepared from medicinal materials according to traditional medicinal theories and methods of oriental countries.

6. Vaccine means an antigen-containing preparation which can make a body immune and is used for disease prevention.

7. Biological means a product of biological origin which is used for human disease prevention, treatment or diagnosis.

8. Active ingredient means a substance or a mixture of substances with disease treatment activity which is used in the manufacture of drugs.

9. New active ingredient means an active ingredient contained in the composition of a drug registered for the first time for circulation in Vietnam.

10. New drug means a drug registered for the first time in Vietnam, including:

a/ Drugs containing new active ingredients;

b/ Drugs with a new combination of active ingredients already circulated in Vietnam.

11. Finished drug means a drug having gone through all processes of manufacture, including the packing of drugs in final packings and labeling.

12. Generic drug means a finished drug used to replace an invented drug which is manufactured without the inventor's franchise license and put into the market after the patent has or monopolies have expired.

13. Drug manufactured under franchise means a drug already granted a registration number for circulation (in Vietnam or overseas) which the domestic or foreign manufacturer transfers the right to manufacture to another eligible manufacturer in Vietnam.

14. Trade name of a drug means a drug's name different from its original name or international nonproprietary name.

15. ASEAN common technical dossier (ACTD) means a set of documents guiding drug registration dossiers to meet common technical requirements of the Association of Southeast Asian Nations (ASEAN).

16. Re-registration means the submission of a registration dossier for a drug when its circulation registration number becomes invalid.

17. Change means any difference in a drug or drug material already granted a registration number, including changes in formula, method of manufacture, place of manufacture, standards of finished products or materials, packings or labels, and product information.

18. Major change means a change which is likely to affect any of the following elements of a drug already granted a circulation registration number:

a/ Indications:

b/ Route of administration;

c/ Concentration, content;

d/ Changes other than minor changes.

19. Minor change means a change which does not affect any of the following elements of a drug already granted a circulation registration number:

a/ Indications;

b/ Route of administration;

c/ Concentration, content;

d/ Dosage;

e/ Active ingredients.

20. Other change means a change other than those referred to in Clauses 18 and 19 of this Article.

21. Country of origin means a country manufacturing final preparations and/or product lots for ex-factory delivery or a country from which a product is transported to the country of importation.

22. Registration establishment means an establishment applying for a circulation license or submitting updated or modified documents of drugs already granted registration numbers.

23. Manufacturer means an establishment performing at least one stage of manufacture and/ or ex-factory delivery of finished products.

Article 3. Prohibited acts

1. Forging or deliberately modifying dossiers, documents or legal papers of Vietnamese or foreign functional management agencies.

2. Using fake seals or forging signatures or seals of registration establishments, manufacturers or relevant establishments in drug registration dossiers.

Article 4. Provisions on drug registration establishments

1. A drug registration establishment must possess a certificate of eligibility for drug trading in Vietnam, for Vietnamese drug trading establishments, or a registration license for operation in the field of drugs or drug materials in Vietnam, for foreign drug trading establish­ments, under the Health Ministry's regulations.

2. A drug registration establishment has the following rights and responsibilities:

a/ To be guided on drug registration and provided with information relating to the drugs it registers:

b/ To apply for the withdrawal of registration numbers of the drugs it registers when necessary (made according to a set form):

c/ To lodge complaints about competent agencies' decisions related to the grant of drug circulation registration numbers. The order, procedures and competence to lodge these complaints comply with the law on complaints and denunciations;

d/ To take responsibility for the quality, safety and effectiveness of drugs and ensure the circulation of drugs according to registration dossiers;

e/ To take responsibility for all the information provided in registration applications or documents in dossiers. To ensure the provision of sufficient data, reports and information relating to the effects and dangers of drugs at the time of submission of registration dossiers to the Drug Administration of Vietnam;

f/ To provide information relating to the submitted data or provide additional information for consideration in the process of drug registration and circulation at the request of the Drug Administration of Vietnam;

g/ To report to the Drug Administration of Vietnam on new information relating to drug quality, safety and effects if this information has not yet been updated in the submitted dossiers and/or is being examined by the Drug Administration of Vietnam as well as when the drugs are in market circulation; information on and changes in sold drugs against registration dossiers within the validity duration of circulation registration numbers, including changes not subject to registration under Appendix II to this Circular (not printed herein):

h/ To notify the Drug Administration of Vietnam and concerned state management agencies of the cases in which circulation permits for drugs with valid registration numbers for circulation in Vietnam are revoked in any country in the world, clearly stating the reason;

i/ To coordinate with importers and manufacturers in recalling from the market the drugs which fail to satisfy quality, safety and effect at the request of management agencies or when so detected by the registration establishments or manufacturers; to report recall results and propose solutions;

j/ To annually report in writing to the Drug Administration of Vietnam on the registered drugs in circulation; to explain cases in which drugs have been registered but are not manufactured (for domestic drugs) or imported (for foreign drugs), made according to a set form;

k/ To archive complete dossiers and supply them to competent state management agencies upon request;

l/ To cooperate in and create conditions for the inspection and evaluation of manufacturers at the request of the Drug Administration of Vietnam; to pay funds for such inspection and assessment before or after the drugs are granted registration numbers for circulation in Vietnam.

Article 5. Provisions on drug manufacturers

1. A domestic drug manufacturer must possess a drug trading eligibility certificate and a certificate of satisfaction of "Good manufacture practices (GMP)" standards under the Health Ministry's regulations on and roadmap for GMP application.

2. A foreign drug manufacturer must satisfy "Good manufacture practices" standards which are equivalent to or higher than "Good manufacture practices" principles and standards as recommended by the World Health

Organization (GMP-WHO). In case GMP standard satisfaction certificates or certificates of pharmaceutical products (CPP) do not indicate that manufacturers satisfy GMP-WHO principles and standards, registration establishments shall provide proof that GMP principles and standards they have satisfied are not lower than GMP-WHO principles and standards. For in-vitro diagnosis biologicals, a manufacturer must satisfy GMP or ISO standards or possess another equivalent certificate. When necessary, the Drug Administration of Vietnam shall evaluate and inspect manufacturers before or after the grant of circulation registration numbers.

3. Drugs must be manufactured at establishments possessing manufacture licenses granted by competent agencies, which have been invested and built to satisfy manufacture conditions under Clause 2 of this Article (except drugs manufactured in the form of processing). Drugs must not be manufactured at other establishments in the form of loan license.

4. A drug manufacturer has the following rights and responsibilities:

a/ To be guided on drug registration and provided with information relating to the drugs it manufactures which are registered in Vietnam;

b/ To request the withdrawal of registration numbers of the drugs it manufactures in case of any problem in the quality, safety and effects of the drugs, affecting users' health, without obtaining approval of registration establishments (made according to a set form);

c/ To lodge complaints about competent agencies' decisions relating to the grant of drug circulation registration numbers. The order, procedures and competence to lodge complaints comply with the law on complaints and denunciations;

d/ To take responsibility for the quality, safety and effects of drugs and ensure the manufacture of drugs according to registration dossiers already approved by the Ministry of Health;

e/ To coordinate with drug importers and registration establishments in withdrawing from the market drugs which fail to ensure quality, safety and effects at the request of management agencies or when so detected by the registration establishments or manufactures; to report withdrawal results and propose solutions;

f/ To coordinate with registration establishments in reporting to the Drug Administration of Vietnam and concerned agencies on any new information relating to the quality, safety and effects of drugs if this information has not yet been updated in the submitted dossiers and/or is being examined at the Drug Administration of Vietnam as well as when the drugs are in market circulation; and on changes in drugs currently in circulation against registration dossiers within the validity duration of circulation registration numbers, including changes not subject to registration under Appendix II to this Circular (not printed herein);

g/ To notify cases in which circulation permits for drugs with valid circulation-registration numbers are revoked in any country in the world to the Drug Administration of Vietnam and concerned state management agencies, clearly stating the reason:

h/ To archive sufficient dossiers of manufactured drugs and supply them to competent state management agencies upon request;

i/ To prepare sufficient working facilities and conditions for the inspection and assessment of manufacturers at the request of the Drug Administration of Vietnam; to coordinate with drug registration establishments in paying funds for such inspection and assessment before or after the drugs are granted registration numbers for circulation in Vietnam.

Article 6. Provisions on establishments franchising or franchised to manufacture drugs: and on processed drugs

1. For pharmaceutical drugs, vaccines, antigen-containing sera and biologicals, franchising and franchised establishments must at least satisfy GMP-WHO standards: for in-vitro diagnosis biologicals. these establishments must satisfy GMP. ISO or other equivalent standards.

2. For oriental medicaments, drugs from medicinal materials and drug materials:

a/ Overseas franchising establishments must at least satisfy GMP-WHO standards. Domestic franchising establishments shall comply with the Health Ministry's roadmap for GMP application;

b/ Franchised establishments shall comply with the Health Ministry's roadmap for GMP application.

3. For drugs manufactured in the form of processing, franchising and franchised establishments shall comply with the Health Ministry's current regulations on drug processing.

Article 7. Requirements on drug test slips

1. For pharmaceutical drugs, biologicals, oriental medicaments and drugs from medicinal materials:

a/ Drug manufacturers satisfying GMP standards shall themselves conduct standard-based appraisal and tests and include their test slips in the registration dossiers to be submitted;

b/ In case domestic drug manufacturers do not yet satisfy GMP standards, drug registration establishments shall conduct standard-based appraisal at any of central state drug-testing establishments or drug-test service providers possessing drug trading eligibility certificates and satisfying professional criteria prescribed by the Ministry of Health.

2. For vaccines, antigen-containing sera and in-vitro diagnosis biologicals:

a/ Establishments registering vaccines or antigen-containing sera shall conduct standard-based appraisal and submit test slips of the National Institute for Control of Vaccines and Biologicals.

b/ Manufacturers registering in-vitro diagnosis biologicals may use their test slips in the circulation registration dossiers to be submitted if they satisfy GMP or other equivalent standards. In case manufacturers do not yet satisfy GMP. ISO or other equivalent standards, registration establishments shall conduct standard-based appraisal and submit test slips of the National Institute for Control of Vaccines and Biologicals.

3. In the process of appraising drug registration dossiers, drug registration establishments shall, at the request of the Drug Administration of Vietnam, re-appraise standards and testing methods at testing establishments designated by the Ministry of Health. Cases subject to re-appraisal are specified in Appendix IV to this Circular (not printed herein).

Article 8. Clinical trial requirements relating to registration of new drugs

Upon registration for circulation in Vietnam, new drugs are subject to clinical trial under the Health Ministry's regulations on clinical trial.

Article 9. Requirements on drug bioavailability and bioequivalence

The submission of research reports and data on bioavailability and bioequivalence of drugs to be registered for circulation complies with the Health Ministry's regulations on submission of research reports and data on bioavailability and bioequivalence.

Article 10. Provisions on languages, form of dossiers, drug samples and fees

1. Languages used in registration dossiers:

a/ Dossiers of registration of domestically manufactured drugs must be written in Vietnamese;

b/ Dossiers of registration of foreign drugs must be written in Vietnamese or English. For dossiers in English, information in use instruction sheets, summary of product properties or information for patients must be in Vietnamese.

2. Drug registration dossiers must be made in A4-size papers and securely bound. A dossier must be arranged in the order of its contents and separated between different parts. Separated parts must be numbered for easy reference, each part having the certification of the drug registration establishment or manufacturer on its first page.

3. Each drug must have a separate registration dossier, except drugs sharing all the elements below which may be registered in the same dossier:

a/ Name of the drug;

b/ Form of preparation;

c/ Formula for a unit of dosage (for drugs with single dosage) or the same concentration and content (for drugs with multiple dosages);

d/ Manufacturer;

4. Common requirements for documents to be submitted in the first-time registration dossiers, re-registration dossiers and dossiers of request for other changes:

a/ One set of originals, for all dossiers specified in Clauses 1 and 2, Article 17, for pharmaceutical drugs, vaccines, antigen-containing sera and biologicals (except in-vitro diagnosis biologicals); Clauses 1 and 2, Article 22, for in-vitro diagnosis biologicals; or Clauses 1 and 2, Article 26, for drugs from medicinal materials, oriental medicaments and drug materials;

b/ Two copies of documents, comprising drug registration applications and finished-product standards;

c/ Drug labels: 2 sets of design specimen labels; for foreign drugs, drug labels must be accompanied by one set of original labels of the drugs currently in circulation in the country of origin. These labels shall be stuck on A4-size papers with seals appended on every two adjacent pages by the drug registration establishment or manufacturer;

d/ Product information: use instructions or information for patients or a summary on product properties comply with regulations applicable to each type of drug, with seals appended on every two adjacent pages by the drug registration establishment or manufacturer;

e/ Drug samples, drug materials:

- One unit of packing, for each specification registered for circulation;

- A volume sufficient for 3 times of testing, for drug materials;

- For vaccines and antigen-containing sera, registration establishments shall deposit their samples at the National Institute for Control of Vaccines and Biologicals;

f/ Summary on products (made according to a set form).

5. For dossiers of registration of major and minor changes: one set of originals of documents, depending on major or minor changes under Clauses 4 and 5, Article 17. for pharmaceutical drugs, vaccines, antigen-containing sera and biologicals; Clauses 3 and 4, Article 22, for in-vitro diagnosis biologicals; or Clauses 3 and 4, Article 26, for drugs from medicinal materials, oriental medicaments and drug materials.

6. Provisions on legal dossiers:

a/ For certificates of pharmaceutical products (CPP), free sale certificates (FSC), certificates of satisfaction of GMP standards or certificates of satisfaction of equivalent standards for in-vitro diagnosis biologicals, their originals, copies or Vietnamese translations may be submitted, but specific provisions of Points b. c or d of this Clause applicable to each kind of certificate and the following general provisions must be complied with:

- For submitted originals: The original must bear the signature, full name and title of the signer and the certification seal of the certificate-granting competent agency of the host country; and must be consularly legalized at the Vietnamese diplomatic representative mission under the law on consular legalization, unless legal papers are granted by competent agencies of the countries that have signed judicial assistance agreements with Vietnam.

- For submitted copies: They shall be lawfully certified by a Vietnamese competent agency under Vietnamese law on certification of copies from originals.

- For submitted Vietnamese translations of foreign-language certificates: They must be certified under regulations by a notary public (i.e., local notary public office, diplomatic representative mission, consular office or another authorized foreign agency, which certifies the translator's signature under law) and enclosed with the originals or copies of certificates under the above regulations.

- The validity term of a certificate must be indicated in the certificate and must remain valid at the time of appraisal; an official letter extending this certificate is not accepted. For certificates not indicating a validity term, only those granted within 24 months from the date of grant may be accepted.

b/ In addition to the requirements specified at Point a of this Clause, a CPP must satisfy the following conditions:

- It must bear a certification that drugs are permitted for circulation in the country of origin. If drugs are not circulated in the country of origin, the registration establishment must explain the matter to the Ministry of Health for consideration;

- In case a drug is manufactured through various stages in different countries, making it impossible to identify the sole country of origin, the drug registration establishment shall submit the CPP of the country manufacturing the final preparations or of the country of ex-factory delivery of the drug lots. If no CPP of these countries of origin is available, the Ministry of Health shall consider and accept the CPP of the country from which the products are transported to the country of importation;

- If no CPP of the above countries is available, only CPP granted by a competent agency of the UK, France, Germany, the US, Japan, Australia or Canada, or by an European Medicine Agency (EMEA);

It is issued by the competent pharmaceutical management agency (on the WHO list at http://www.who.int) of the country of origin according to WHO form, applicable to the system of quality certification of pharmaceutical products sold in international trade.

c/ In addition to the requirements specified at Point a of this Clause, an FSC must satisfy the following conditions:

- It must bear a certification that drugs are permitted for circulation in the country of origin. If drugs are not circulated in the country of origin, the registration establishment must explain the matter to the Ministry of Health for consideration;

- It is granted by a competent agency of the country of origin, containing sufficient information on the composition and form of preparation of the drugs and the validity term of the FSC.

d/ GMP-WHO certificates, ISO certificates or certificates of satisfaction of equivalent standards must be granted by competent agencies of countries of origin, with their certification of the names and addresses of manufacturers.

e/ Drug trading eligibility certificates must remain valid and be originals or copies certified by competent state certification agencies in Vietnam and granted by competent agencies under current regulations.

f/ Foreign enterprises' operation licenses for drugs and drug materials in Vietnam must remain valid and be originals or copies certified by overseas registration establishments or their Vietnam-based representative offices;

g/ Certificates, protection titles and ownership transfer contracts for related industrial property objects in drug registration dossiers (if any), granted or certified by competent industrial property agencies, must be originals or copies appended with seals of drug registration establishments.

7. Provisions on other administrative dossiers:

a/ Registration applications must be hand-signed by directors or authorized representatives of drug registration establishments and appended with seals (if any) of these establishments. Seal-engraved signatures are not accepted.

b/ Authorization papers shall be made according to Form 3/TT to this Circular (not printed herein) and submitted in the following cases:

- Authorization in the name of the registration establishment (form 3A);

- Authorization by the drug registration establishment for its Vietnam-based representative office to sign the drug registration dossier (form 3B);

- Authorization for the use of names of the drugs with registered trademarks in case the trademark owner is other than the drug registration establishment (form 3C).

Each dossier must be enclosed with an authorization paper, which is the original or a copy certified as true copy by the drug registration establishment or its Vietnam-based representative office.

c/ Copies of franchise contracts, for drugs manufactured under franchise.

8. Provisions on drug labels and product information:

The details of drug labels and product information comply with the Health Ministry's current regulations on labeling of drugs and/or ACTD regulations.

9. Provisions on fees:

Drug registration establishments shall pay fees related to drug registration and circulation under the current law on charges and fees.

Article 11. Provisions on naming of drugs

1. The Ministry of Health encourages registration establishments to use international nonproprietary names (INN) for drugs.

2. In case a drug is not given an INN, the drug registration establishment may use trade name but shall adhere to the following principles:

a/ Not exaggerating the drug's treatment effect;

b/ Not untruthfully reflecting the drug's treatment effect; not causing confusion about the drug's pharmaco-physical effects. Drugs with different active ingredients must have different names;

c/ Not breaching Vietnam's fine customs and traditions;

d/ Not causing conflicts to protected intellectual property objects of other individuals or organizations;

e/ Not being identical with or similar to the names of other establishments' drugs already granted registration numbers.

Article 12. Forms of drug registration

Pharmaceutical drugs, biologicals, vaccines, antigen-containing sera, in-vitro diagnosis biologicals. oriental medicaments, drugs from medicinal materials and drug materials shall be registered in the following forms:

1. First-time registration;

2. Registration of major changes;

3. Registration of minor changes;

4. Re-registration.

Article 13. Validity of drug registration numbers

The maximum validity duration of a drug circulation registration number is 5 years from the signing date of the decision to grant such number. In special cases, the Ministry of Health shall consider and issue separate regulations. Within 6 months before or after a circulation registration number becomes invalidated, an establishment may submit a re-registration dossier. Past this time limit, the establishment shall submit dossiers like in the case of first-time registration.

Chapter II

INTELLECTUAL PROPERTY FOR REGISTERED DRUGS

Article 14. General principles

1. Drug registration establishments shall take responsibility for issues relating to intellectual property of drugs registered for circulation.

2. The Ministry of Health encourages drug registration establishments to establish intellectual property rights or inquire about related intellectual property objects before registering the circulation of drugs in Vietnam.

3. If there arises an intellectual property-related dispute in the course of consideration for the grant of a circulation registration number, the party objecting to the grant of a registration number for the disputed drug shall supply infringement-related conclusions of the intellectual property state management agency or the agency functioning to enforce intellectual property rights. The Ministry of Health may refuse to grant a registration number for the drug if having sufficient grounds for believing that the drug, once granted a registration number, is likely to infringe upon protected intellectual property rights of other individuals or establishments.

4. If there arises an intellectual property-related dispute following the grant of a circulation registration number, the Ministry of Health shall, at the proposal of the holder of intellectual property rights or a third party with related interests and based on the court verdict or infringement-related final conclusions of the state management agency in charge of intellectual property or agency functioning to enforce intellectual property rights, decide to suspend the circulation or withdraw the circulation registration number of the drug concluded as infringing upon intellectual property rights.

Article 15. Inventions related to registered drugs

1. For drugs containing active ingredients still in the period of intellectual property protection, registration establishments may supply legal documents relating to the protection and intellectual property rights (patent) of registered drugs (if any).

2. Within 2 years before the expiration of the invention protection duration for a drug, the drug registration establishment may submit a dossier of registration for circulation of generic drugs, enclosed with documents evidencing that the validity duration of the protected drug is going to expire, and shall clearly state its request in the registration application (made according to a set form).

Article 16. Data confidentiality for registration dossiers

Drug registration establishments that wish to have data in their new drug registration dossiers kept confidential shall comply with the Health Ministry's regulations on data confidentiality for drug registration dossiers and clearly state such request in their registration applications (made according to a set form).

Chapter III

SPECIFIC PROVISIONS ON DRUG REGISTRATION DOSSIERS

Section 1. REGISTRATION DOSSIERS FOR FINISHED PHARMACEUTICAL DRUGS, VACCINES, ANTIGEN-CONTAINING SERA AND BIOLOGICALS

Article 17. Dossiers to be submitted

1. First-time registration dossiers for new pharmaceutical drugs, vaccines, antigen-containing sera or biologicals, comprising:

a/ Part I. Administrative dossier and product information:

b/ Part II. Quality dossier:

c/ Part III. Pre-clinical dossier;

d/ Part IV. Clinical dossier.

2. First-time registration dossiers for generic drugs (applicable only to pharmaceutical drugs), comprising:

a/ Part I. Administrative dossier and product information;

b/ Part II. Quality dossier.

3. Re-registration dossiers, comprising:

a/ Part I. Administrative dossier and product information;

b/ Part II. Quality dossier;

c/ Part III. Circulation report (made according to a set form).

4. Dossiers of registration of major changes:

a/ Part I. Administrative dossier and product information;

b/ Part II. Quality dossier;

c/ Part III. Clinical dossier.

The details of major changes and relevant dossiers to be submitted are guided in Section I. Appendix II to this Circular (not printed herein).

5. Dossiers of registration of minor changes:

a/ Part I. Administrative dossier and product information;

b/ Part II. Quality dossier;

The details of minor changes and relevant dossiers to be submitted are guided in Section II, Appendix II to this Circular (not printed herein).

6. Dossiers of registration of other changes are guided in Section III, Appendix II to this Circular (not printed herein).

7. For the dossiers specified in Clauses 1 thru 6 of this Article:

a/ They must comply with the provisions in Appendix I to this Circular (not printed herein), including:

- ACTD;

- Guidance on stability research;

- Guidance on appraisal of the manufacturing process;

- Guidance on appraisal of analysis methods;

- Guidance on bioavailability and bioequivalence research;

b/ They must be made according to the ACTD's form. Dossiers of new pharmaceutical drugs, vaccines, antigen-containing sera and biologicals which cannot be made according to the ACTD's form may be made like common technical dossiers of the International Conference on Harmonization (ICH-CTD).

8. For processed drugs, requirements on dossiers to be submitted comply with the Health Ministry's current regulations on drug processing.

Article 18. Specific provisions on administrative dossiers and product information

An administrative dossier and product information comprise:

1. Cover, made according to a set form;

2. Table of contents;

3. Registration application, made according to a set form;

4. Authorization paper (if any), made according to a set form;

5. Operation license for drugs and drug materials, for foreign drug trading establishments in Vietnam, or drug trading eligibility certificates, for Vietnamese drug trading establishments;

6. CPR made according to a set form, for foreign drugs;

7. FSC, for foreign drug registration establishments possessing no CPPs;

8. GMP certificate of the domestic drug manufacturer or of the foreign drug manufacturer, if the drug registration establishment submits the FSC or CPP without certification of the satisfaction of GMP standards. In case more than one manufacturer is involved in the process of drug manufacture, the drug registration establishment shall submit GMP certificates of all the manufacturers involved in the process of manufacturing finished products;

9. Drug label;

10. Product information:

a/ Use instructions, for generic drugs:

b/ Summary on product properties, for new pharmaceutical drugs, vaccines, antigen-containing sera and biologicals, made according to a set form;

c/ Information for patients, for drugs requiring no prescription, made according to a set form.

11. Report on the circulation of drugs, for re-registration dossiers, made according to a set form;

12. Franchise agreement or contract, for drugs manufactured under franchise;

13. Certificates, protection titles and right transfer contracts, for related industrial property objects (if any):

14. Other legal papers (if any).

Article 19. Specific provisions on quality dossiers

A quality dossier is guided in Part II-ACTD and comprises:

1. Table of contents;

2. Summary on quality;

3. Contents and data;

4. Documents for reference;

5. The manufacturer's general dossiers, made according to a set form. In case a product is manufactured in more than one stage, the general dossiers must be dossiers of all the manufacturers involved in manufacturing the product before
putting it into the market.

Article 20. Specific provisions on pre-clinical dossiers

A pre-clinical dossier is guided in Part III-ACTD and comprises:

1. Table of contents;

2. General pre-clinical research;

3. Summary on pre-clinical research;

4. Report on pre-clinical research;

5. Documents for reference.

Article 21. Specific provisions on clinical dossiers

A clinical dossier is guided in Part IV-ACTD and comprises:

1. Table of contents;

2. Clinical overview;

3. Clinical summary;

4. List of clinical researches;

5. Report on clinical research;

6. Documents for reference.

Section II. DOSSIERS OF REGISTRATION OF IN-VITRO DIAGNOSIS BIOLOGICALS

Article 22. Dossiers to be submitted

1. First-time registration dossiers for diagnosis biologicals. including semi-finished products, comprising:

a/ Part I. Administrative dossier;

b/ Part II. Quality dossier;

c/ Part III. Dossier of diagnosis efficiency, not applicable to semi-finished products;

2. Re-registration dossiers, comprising:

a/ Part I. Administrative dossier;

b/ Part II. Quality dossier;

c/ Part III. Circulation report, made according to a set form.

3. Dossiers of registration of major changes comply with provisions applicable to first-time registration as guided in Appendix III B to this Circular (not printed herein).

4. Dossier of registration of minor changes, comprising:

a/ Registration application (made according to a set form);

b/ Change-related dossiers as specified in Appendix III A to this Circular (not printed herein).

Article 23. Specific provisions on administrative dossiers and product information

An administrative dossier comprises:

1. Cover, made according to a set form;

2. Table of contents;

3. Registration application, made according to a set form;

4. Product label;

5. Authorization paper (if any), made according to a set form;

6. Operation license in Vietnam for vaccines and biologicals, granted by a competent agency, if the registration establishment is a foreign enterprise; or certificate of eligibility for trading in vaccines and biologicals, if the registration establishment is a Vietnamese enterprise;

7. License for circulation of products in the country of origin, for foreign products (not applicable to semi-finished products);

8. GMP or ISO certificate or certificate of satisfaction of equivalent standards of manufacturers involved in the manufacturing process, granted by a competent agency;

9. Intellectual property certificate, economic contract and other papers (if any).

The dossier details are guided in Appendix III A to this Circular (not printed herein).

Article 24. Specific provisions on quality dossiers

A quality dossier comprises:

1. Table of contents;

2. Components of active ingredients;

3. Finished products;

4. Stability.

The dossier details are guided in Appendix III A to this Circular (not printed herein).

Article 25. Specific provisions on dossiers of effect evaluation of diagnosis biologicals

A dossier of effect evaluation of diagnosis biologicals comprises:

1. Table of contents;

2. Research reports.

3. The dossier details are guided in Appendix III A to this Circular (not printed herein).

Section III. DOSSIERS OF REGISTRATION OF DRUGS FROM MEDICINAL MATERIALS, ORIENTAL MEDICAMENTS AND DRUG MATERIALS

Article 26. Dossiers to be submitted

1. First-time registration dossiers, comprising:

a/ Administrative dossier and product information;

b/ Quality dossier;

c/ Safety and effect dossier, applicable only to new drugs and new drug materials.

2. Re-registration dossiers, comprising:

a/ Administrative dossier and product information;

b/ Quality dossier;

c/ Circulation report, made according to a set form.

3. Dossiers of registration of major changes: Details of major changes and dossiers to be submitted are guided in Section I. Appendix II to this Circular (not printed herein).

4. Dossiers of registration of minor changes: Details of minor changes and dossiers to be submitted are guided in Section II, Appendix II to this Circular (not printed herein).

5. Dossiers of registration of other changes, which are guided in Section III. Appendix II to this Circular (not printed herein).

Article 27. Specific provisions on administrative dossiers and product information

Administrative dossiers and product information are specified in Article 18 of this Circular.

Article 28. Specific provisions on quality dossiers

1. Manufacturing process a/ Materials:

- For drugs from medicinal materials and oriental medicaments: The manufacturing process is not required for excipient and materials named in the pharmacopoeia and materials manufactured by other manufacturers. In other cases, the process of manufacturing materials must be described in full and detail.

- For drug materials: The process of manufacturing materials must be described in full and detail.

b/ Finished products:

- Formula for the smallest unit of packing: names of materials, including main components and excipient; content or concentration of each material; materials' applicable standards. If finished products are manufactured from bone glue, the quantity of medicinal materials must be indicated;

- Formula for a lot or batch of manufacture: names of materials, including main components and excipient; weight or volume of each material;

- Diagram of the manufacturing process, including all stages;

- Description of the manufacturing process: to describe in full and detail each stage in the manufacturing process;

- List of equipment and instruments used: names of equipment, specifications and use purposes;

- Control in the manufacturing process: to describe in full and detail the criteria for inspection and control in the manufacturing process.

2. Quality standards and testing methods

a/ For drug materials named in the pharmacopoeia, to indicate the name of the pharmacopoeia and year of publication. For those not named in the pharmacopoeia, to describe in full and detail the testing criteria and methods.

b/ Finished products:

- Formula for the smallest unit of packing: names of materials, including main components and excipient; content or concentration of each material; materials' applicable standards. If finished products are manufactured from bone glue, the quantity of medicinal materials must be indicated;

- Finished-product standards: to describe in full and detail the finished products' testing criteria and methods.

c/ Packing standards: to describe in full and details the testing criteria and methods.

d/ Drug test slips are specified in Article 7 of this Circular.

e/ Stability research documents, comprising:

- Stability research plan;

- Stability research data;

- Stability research conclusions.

Article 29. Specific provisions on safety and effect dossiers

Safety and effect dossiers of new drugs comply with the Health Ministry's regulations on clinical testing, comprising:

1. Reports on toxicity;

2. Reports on clinical research, not applicable to cases of registration of materials.

Chapter IV

ORDER OF AND PROCEDURES FOR DRUG REGISTRATION, AND COMPETENCE TO GRANT, SUSPEND AND WITHDRAW REGISTRATION NUMBERS

Article 30. Order of and procedures for receiving and appraising drug registration dossiers

1. The Drug Administration of Vietnam under the Ministry of Health shall receive drug registration dossiers submitted directly to it or by post in the following cases:

a/ Drug first-time registration and re-registration dossiers, except those specified in Clause 2 of this Article;

b/ Dossiers of registration of major changes, minor changes or other changes within the validity duration of circulation registration numbers of drugs, for all drugs with registration numbers.

2. Provincial-level Health Departments of the localities in which manufacturers are based shall receive first-time registration and re-registration dossiers submitted directly to them or by post, for domestically manufactured drugs for external use as specified in Appendix V to this Circular (not printed herein).

3. The Drug Administration of Vietnam shall appraise the dossiers specified at Point a, Clause 1 of this Clause and submit them to the Advisory Council for the Grant of Drug Registration Numbers under the Ministry of Health; issue written replies to requests for major changes, minor changes or other changes, for drugs with registration numbers which remain valid under Point b. Clause 1 of this Article.

4. Provincial-level Health Departments shall appraise dossiers specified in Clause 2 of this Article and send official letters enclosed with lists of drugs to the Drug Administration of Vietnam, requesting the grant of registration numbers.

Article 31. Competence to grant registration numbers

1. The Minister of Health may authorize the director of the Drug Administration of Vietnam to sign decisions promulgating lists of drugs to be granted registration numbers for:

a/ Drug registration dossiers received and appraised by the Drug Administration of Vietnam under Point a. Clause 1, Article 30 of this Circular;

b/ Drug registration dossiers received and appraised by provincial-level Health Departments under Clause 2, Article 30 of this Circular.

2. The Drug Administration of Vietnam shall issue written replies to requests for major changes, minor changes or other changes, for drugs with registration numbers which remain valid under Point b. Clause 1 of Article 30; and settle matters related to drug manufacture, registration and circulation.

Article 32. Time limit for granting registration numbers or issuing replies for dossiers of registration of major changes, minor changes or other changes

1. Within 6 months after receiving complete and valid dossiers, the Ministry of Health shall grant circulation registration numbers for drugs registered for the first time or re-registered. In case the conditions for such grant are not or not yet fully satisfied, it shall issue written replies clearly stating the reason.

2. Within 3 months after receiving complete and valid dossiers, provincial-level Health Departments shall examine them and send official letters enclosed with lists of drugs requested for the grant of circulation registration numbers under Clause 2, Article 30 to the Ministry of Health for consideration and grant of circulation registration numbers. If having insufficient grounds for the grant of circulation registration numbers, provincial-level Health Departments shall issue written replies to registration establishments, clearly stating the reason.

3. Within 2 months after receiving complete and valid dossiers, the Ministry of Health shall examine them and issue written replies for dossiers of registration of major changes or minor changes.

4. For requests for other changes, their dossiers are the same as re-registration dossiers and the time limit for issuing replies is prescribed in Clauses 1 and 2 of this Article.

5. The Ministry of Health shall consider and grant registration numbers or issue written replies before the expiration of the time limit specified in Clauses 1 and 3 of this Article at the proposal of registration establishments in the following cases:

a/ Drugs meeting special treatment requirements on the Health Ministry's list of rare drugs;

b/ Drugs meeting treatment requirements in cases of emergency, natural disasters or epidemics;

c/ Drugs domestically manufactured on GMP-standard new chains within 18 months from the date of grant of GMP certificates.

For drugs registered under Clause 5 of this Article, drug registration establishments shall clearly state in registration applications the requests for priority consideration and grant of registration numbers (made according to a set form).

6. The Drug Administration of Vietnam shall establish procedures to specify the supplementation of drug registration dossiers to suit practical conditions in each period.

Article 33. Cases subject to withdrawal of registration numbers of drugs

Within the validity duration of registration numbers, the Ministry of Health shall consider and decide to withdraw registration numbers for drugs with circulation registration numbers in the following cases:

1. Drugs manufactured not according to circulation registration dossiers already approved by the Ministry of Health, except cases permitted by the Ministry of Health;

2. Drugs with 2 manufactured lots failing to satisfy quality standards or drugs once seriously breaching quality standards as concluded by a state management agency in charge of drug quality;

3. Manufacturers or registration establishments requesting the withdrawal of registration numbers for circulation of drugs in Vietnam;

4. Drugs with registration numbers withdrawn in host countries;

5. Drugs containing active ingredients which are unsafe for users as recommended by the WHO and/or competent Vietnamese or foreign functional agencies;

6. Drugs concluded by competent agencies to infringe upon intellectual property rights.

Article 34. Cases subject to suspension of receipt of drug registration dossiers and grant of registration numbers for submitted dossiers

1. The Ministry of Health will suspend receiving drug registration dossiers and granting registration numbers for the submitted dossiers in the following cases:

a/ Drug registration establishments and/or manufacturers having 2 or more drugs suspended from circulation for one year;

b/ Drug registration establishments and/or manufacturers with drugs having registration numbers withdrawn for breaching Clause 1,5 or 6. Article 33 of this Circular; or falling into the case specified in Clause 4, Article 33 of this Circular, without notifying such to the Ministry of Health;

c/ Drug registration establishments and/or manufacturers committing any of the prohibited acts defined in Article 3 of this Circular;

d/ Drug registration establishments and/or manufacturers providing dossiers, data and information relating to technical dossiers, including quality standard, manufacturing methods and stability, without basing on their practical research, experiment or manufacture conditions;

e/ Drug registration establishments and/or manufacturers providing dossiers, data and information on drugs' effects and safety without scientific documents or proof;

f/ Drug registration establishments and/or manufacturers submitting samples of to-be-registered drugs other than those indicated by them in their manufacture registration dossiers.

2. Drug registration establishments and/or manufacturers falling into the case specified at Point c. Clause 1 of this Article are also subject to criminal or administrative handling under current relevant laws.

Article 35. Competence to decide, responsibility to notify, and time limit for withdrawing circulation registration numbers or suspending the receipt of dossiers or grant of circulation registration numbers for drugs

1. The Minister of Health may authorize the director of the Drug Administration of Vietnam to decide to withdraw circulation registration numbers or suspend receiving dossiers or granting registration numbers nationwide.

2. Provincial-level Health Departments and health agencies of sectors may notify their decisions withdrawing registration numbers or suspending the receipt of dossiers or grant of registration numbers in localities under their management.

3. The maximum time limit for suspending the receipt of drug registration dossiers and grant of circulation registration numbers for the submitted dossiers is 2 years, for cases specified at Points a. b and c. Clause 1, Article 34 of this Circular, from the date of signing second decisions to withdraw registration numbers or suspend the circulation of drugs or handling decisions of competent state management agencies, for establishments committing the acts specified at Point c, Clause 1, Article 34 of this Circular.

4. The maximum time limit for suspending the receipt of drug registration dossiers and grant of circulation registration numbers for the submitted dossiers in the cases specified at Points d, e and f, Clause 1, Article 34 of this Circular is one year from the date of obtaining final notices of the violations of the above regulations committed by registration establishments.

Chapter V

ORGANIZATION AND OPERATION OF APPRAISERS AND THE ADVISORY COUNCIL FOR THE GRANT OF CIRCULATION REGISTRATION NUMBERS FOR DRUGS

Article 36. Organization and operation of the Advisory Council for the Grant of Circulation Registration Numbers for Drugs

1. The Ministry of Health shall set up the Advisory Council for the Grant of Circulation Registration Numbers for Drugs (below referred to as the Advisory Council).

2. The Advisory Council is tasked to advise the Ministry of Health on the grant of registration numbers for drugs to be circulated in Vietnam; policies on harmonization of drug registration regulations with those of regional and world countries; policies on the manufacture, import and circulation of drugs in Vietnam, including the use of drugs on Vietnamese, to evaluate the safety and effects of drugs when necessary.

3. The Advisory Council shall operate on the principle that its advisory opinions must be based on legal and scientific grounds and recorded in minutes of its meetings. The Advisory Council is answerable to the Minister of Health for its advisory opinions relating to drug registration.

4. The Drug Administration of Vietnam shall advise the Minister of Health in promulgating regulations on the organization and operation of the Advisory Council and the mechanism of coordination between the Advisory Council and groups of appraisers in the grant of circulation registration numbers for drugs.

Article 37. Organization and operation of groups of appraisers of drug registration dossiers

1. The Ministry of Health shall assign the Drug Administration of Vietnam to set up groups of appraisers of drug registration dossiers (below referred to as groups of appraisers).

2. Groups of appraisers shall advise the Drug Administration of Vietnam in appraising drug registration dossiers and propose the grant, supplementation of non-grant of registration numbers.

3. Groups of appraisers operate on the principle that appraisers' comments and/or proposals must be based on legal and scientific grounds and written in records of appraisal of drug registration dossiers. Appraisers are answerable to the director of the Drug Administration of Vietnam for their advisory contents/opinions and proposals relating to the appraisal of drug registration dossiers.

4. The Drug Administration of Vietnam shall elaborate and promulgate regulations on criteria for the selection, organization and operation of groups of appraisers; annually sign contracts with appraisers; organize the appraisal and summarize appraisal results for submission to the Advisory Council; organize training courses for appraisers; and evaluate the professional capacity and observance of regulations for replacing or adding appraisers as appropriate.

Chapter VI

ORGANIZATION OF IMPLEMENTATION

Article 38. Effect

1. This Circular takes effect 6 months from the date of its signing.

2. To annul the Health Minister's Decision No. 3121/2001/QD-BYT of July 18, 2001, promulgating the Regulation on registration of drugs; Decision No. 4012/2003/QD-BYT of July 30, 2003, promulgating the Regulation on registration of vaccines and biologicals; and Decision No. 3947/2004/QD-BYT of November 8, 2004, amending and supplementing the Regulation on registration of vaccines and biologicals.

Article 39. Transitional provisions

Drug registration dossiers submitted prior to the effective date of this Circular shall be examined and drugs shall be granted registration numbers under the Regulation on registration of drugs promulgated together with the Health Minister's Decision No. 3121/2001/QD-BYT of July 18, 2001, and the Regulation on registration of vaccines and biologicals promulgated together with Decision No. 4012/2003/QD-BYT of July 30, 2003.

Article 40. Roadmap for application of this Circular

1. From the effective date of this Circular, drug registration establishments shall submit registration dossiers in accordance with this Circular.

2. Before January 1, 2012, if quality dossiers of drugs to be re-registered cannot be prepared according to the ACTD form and ASEAN technical guidelines attached to this Circular (not printed herein), registration establishments may re-submit dossiers containing testing standards and methods like those upon the grant of first-time registration numbers under the Regulation on registration of drugs promulgated together with the Health Minister's Decision No. 3121/ 2001/QD-BYT of July 18, 2001, and the Regulation on registration of vaccines and biologicals promulgated together with Decision No. 4012/2003/QD-BYT of July 30, 2003.

3. Requirements on dossiers of research into drug stability under practical conditions (for new drugs and drugs to be registered for the first time) under ASEAN guidelines are uniformly applicable from January 1, 2011.

4. The Ministry of Health encourages drug registration establishments to submit dossiers in accordance with this Circular before its effective date.

Article 41. Implementation responsibility

1. The Drug Administration of Vietnam shall:

a/ Guide and implement this Circular;

b/ Edit and keep updated ACTDs and enclosed technical guidelines for concerned entities' compliance;

c/ Regularly keeping updated on its website the lists of drugs granted circulation registration numbers by the Ministry of Health (in each drive);

d/ Develop and promulgate Standard Operating Procedures (SOPs) and quality manuals (QMs) and apply them;

e/ Step by step publish on its website the following information relating to drug registration:

- General data of drugs with valid registration numbers;

- Lists of active ingredients still in the period of invention protection;

- Approved drug labels and use instructions;

- Lists of registration establishments and manufacturers violating the provisions of this Circular;

f/ Annually propose, based on the practical grant of circulation registration numbers, appropriate management measures to regulate the drug circulation registration under Vietnamese law and international practice.

2. Provincial-level Health Departments, the Vietnam Pharmacy Corporation, medicinal materials manufacturers and traders, and licensed foreign pharmacy companies shall implement this Circular.

3. Any problems arising in the course of implementation should be promptly reported to the Ministry of Health (the Drug Administration of Vietnam) for consideration and settlement.-

APPENDIX II

MAJOR CHANGES, MINOR CHANGES, AND OTHER CHANGES APPLIED TO REGISTERED DRUGS

(not applied to in-vitro diagnostic reagents)

(enclosed with the Circular No. 22/2009/TT-BYT dated November 24, 2009)

I- MAJOR CHANGES

II- MINOR CHANGES

1- Minor changes subject to approval by regulatory bodies:

2- Minor changes that must be notified to regulatory bodies (and may be made if no opinions are given by regulatory bodies after 14 days):

III- Other changes.

FORM 2B: CHANGE REGISTRATION FORM

A. INFORMATION ABOUT REGISTERING FACILITY AND MANUFACTURING FACILITY

1. Registering facility (FSC holder)

1.1. Name:

1.2. Address:                                                             Website (if any)

1.3. Phone number:                                  Fax:                                       e-mail:

1.4. Representative office or contact in Vietnam:

Name:

Phone number:                                                          Cell phone:

Address:

2. Manufacturing facility (*)

2.1. Name:

2.2. Address:                                                             Website (if any):

2.3. Phone number:                                  Fax:                                       e-mail:

(*) = The manufacturer responsible for the batch

2.4. Other manufacturing facility:

(**) = “processing semi-finished products, “packaging”, “granuling”, “producing raw dosage forms”, "contracted researcher”, “franchise", etc.

B. INFORMATION ABOUT THE PRODUCT:

1. Name, dosage form, and composition of product:

1.1.  Trade name:

1.2.  Dosage form

1.3.  Active ingredient and their contents

1.4.   Registration number:                Date of issue:                Date of expiry:

2. Product description:

2.1.  Description of dosage form:

2.2.  Description of packaging:

2.3.  Classification.

2.4.  Standard quality:

2.5.  Expiry date:

2.6.  Preservation conditions:

3. Generic names, content active ingredients and excipients:

C. MAJOR CHANGES AND MINOR CHANGES:

D. ENCLOSED TECHNICAL DOCUMENTS:

DD. DECLARATION OF APPLICANT:

We, the undersigned, hereby declare that we have checked, add a signature and seal to every relevant parts of the documents included in this dossier, that these papers are legal and truthful, and understand that any inaccurate false or inaccurate information in the form will be the basis for penalty imposition.

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