Regulations on drug registration in Vietnam

Regulation on Drug Registration Page 1 of 47 REGULATION ON DRUG REGISTRATION (Issued in conjunction with decision No3121/2001/QD-BYT dated 18 July 2001 of the Minister of Health) Chapter 1 General provisions Chapter II Application dossiers for registration of domestic drug products Chapter III Application dossiers for registration of imported drug products Chapter IV Application dossiers for registration of drug products manufactured under-license Chapter V Requirements on utilization of drug products for assessment of safety and efficacy on Vietnamese human subjects Chapter VI Infringement settlement Chapter VII Regulation enforcement With the aim to unify the government’s management over production and sale of drugs; to ensure the safety, efficacy and quality of drugs, the MOH hereby promulgates the Regulation on Drug Registration. Chapter 1 GENERAL PROVISIONS Article 1: Drug products produced and sold in Vietnam for purposes of prevention and treatment of diseases and for improvement of the human’s health shall be registered with the Ministry of Health and be approved by the latter to get a registration number. In special cases (drugs for epidemic and disasters relief and orphan drugs) the sale and consumption of un-registered drugs shall be specifically considered and approved by the Ministry of Health. Article 2: Scope of application and objects of the Regulation: 2.1. Scope of application: - Drug products produced by legal domestic and foreign manufacturers who have satisfied conditions in drug production, shall the registered before production and sale; Regulation on Drug Registration Page 2 of 47 - New drug products developed by scientific research institutions, while awaiting technological transferring to any producers with satisfied conditions in drug production, the innovator institutions can apply for registration for their own production and sale, provided that the institutions meet required conditions for drug production. - Drug products produced under-licence can only be produced by a drug producer with GMP standard production facilities located in Vietnam. - Drug products produced and prepared by health care institutions for the use of that institutions or their peripheral stations in therapy (that shall not be sold to the market); Heads of such institutions shall be responsible for drug formula, preparing process, specifications, safety and efficacy of the drugs produced by their institutions. 2.2 Scope of application: The following entities can register drug products for production and sale in Vietnam: - Drug manufactures located in the territory of Vietnam; - Domestic companies having functions in pharmaceutical trading, foreign companies registered to operate in pharmaceutical field in Vietnam; Article 3: In this Regulation, some terms can be interpreted as follows: 3.1. Drugs are products intended for use in human for the purposes of prevention, treatment, relief or diagnosis of diseases or for modification of physiological functions. 3.2. Finished drug products are those drug products that have passed all stages of production and are ready for marketing, distribution and use; 3.3. Starting materials are substances, active (active ingredients) or in-active (reagents, excipients), that are put in compositions of drug products in production process. 3.4. Western drug products include: - pharmaco-chemicals and biologicals used as starting materials for drug production. Regulation on Drug Registration Page 3 of 47 - Finished pharmaco-chemical and biological products. 3.5. Ancient medicines are those that are used following ancient (old) literatures regarding: number of medicinal ingredients, quantity of each ingredient, processing methods, dosage, usage methods and indications. 3.6. New drugs are those with a new active ingredient in their composition; those that are new combination of known active ingredients; or those known drug products with new pharmaceutical dosage forms, new indications or new administration routes. 3.7. A brand name is a name given by a drug manufacturer for a drug product that are different from the generic names or International Non-proprietary Names (INN) internationally or domestically recognized. 3.8. Drug stability is stability of quality of drug products (starting materials or finished products) that, under specified storage conditions, remain their physical, chemical and biological nature, and their characteristics of pharmacology, toxicity, etc. in specified limitations. 3.9. Drug shelf-life is the duration from the time point when a drug product is produced to the predicted time point when the drug product still maintains its quality criteria as required in respective specifications in specified storage conditions. 3.10. Expiration date is a certain validity period from the date of production given to a certain drug product, within which and under specified storage conditions the product still meets required the registered specifications, and after the date the drug product is no longer valid for use. 3.11. A drug product under-licence is a drug product owned by a domestic or a foreign drug entities and has been granted a registration number (in Vietnam or in other countries), the production of which has been authorized by that manufacturer to another legal drug manufacturer in Vietnam. Article 4: An application dossier for registration of a drug product shall be prepared in three sets, including at least one of originals. In the application xie junxiong 附注 1.New Chemical Entity in the world.--Need Phase I-IV Clinical trials. All performed in Vietnam. 2.new in Vietnam--means not registered in Vietnam before.Need phase III or IV--Vietnamese to confirm the dosage and effcicacy and side effects--follow ICH. Has Vietnamese regulations on clinical trial based WHO guideline. --Science & Research Dept under MoH. xie junxiong 附注 From regular tablets to Slow Release or Controlled Release--no need for BA/BE. Change of administration route-clinical trials. From ointment or cream or external use to internal or parenteral---new drugs Regulation on Drug Registration Page 4 of 47 dossier, the followings papers shall be provided with the originals or notarized papers: - Free Sale Certificate (FSC) - Certificate of Good Manufacturing Practices (GMP Certificate) (The FSC and GMP can be replaced with a Certificate of Pharmaceutical Product (CPP)). In addition, two sets of drug labeling shall be attached to the application dossier. The application dossier shall be literally presented on A4-sized paper sheets, in required order, with clear separation between different parts. All the documentation in the dossier shall be certified by manufacturer (with signature and stamp). In case where drug labeling is glued on A4-sized paper sheet, adjoint stamp is required. - Application dossiers of drug manufacturers located on the territory of Vietnam shall be presented in Vietnamese language. Application dossiers of imported drug products shall be presented in Vietnamese language or English. The Summary of Product Characteristics shall be written in Vietnamese language. Name of ingredients of the drug product shall be stated by generic names or international or domestic non-proprietary names. For the ingredients of herbal origin, the names shall be given along with scientific names in Latin. - For a domestic drug products applied with a brand name, the application dossier shall be included a copy of a reference note proving that no similar names have been registered with the Department of Industrial Properties Protection (Ministry of Science, Technology and Environment) or a certificate of industrial properties registration issued by the Department. For imported drug products with marketing authorization in the country of manufacture, reference to the trademark and design by the Department mentioned in the previous paragraph must be made upon request. - A local applicant applying for registration of a drug product as a new drug manufacturer shall provide the following papers: Regulation on Drug Registration Page 5 of 47 ＋ Certificate of operation registration with indication of business functions ＋ Certificate of Good Manufacturing Practices or Certificate of satisfied conditions for manufacturer of medicinal plants or herbal medicines (applied to drug products originated from medicinal plants only). Article 5: Labeling requirements: - Drug labeling shall comply with the Circular on Drug Labeling issued by the MOH and the Regulation on Goods Labeling issued in conjunction with the Decision No: 178/1999/QD-TTg dated 30 August 1999 of the Prime Minister. - Brand-names, principal trademark (language, images or combination of them which is presented with one or more colours) shall not imitate or be confusingly similar to the names or principal trademarks of drug products of other manufacturers that have already been approved by MOH; not infringe to industrial properties rights; not be confusing to the nature of drug product or being exaggerated in presentation and ambiguous to the potency of drug products. The use of generic names or international or national non-propriety names for drug products are encouraged. - Other information, such as bar code, digital code, medals, awards, marks of industrial properties rights to be appeared on the label, should be provided with proper duly proof. - Labels that are officially marketed shall be of the same colour and presentation as those provided in the application dossiers for drug registration. Article 6: In the period of registration validity, a registered drug product shall be applied for registration as a new application if any of the following changes is made: - change of formula and compositions; - change of pharmaceutical dosage form; - change of quality specifications and analytical methods; - change of route of administration; Regulation on Drug Registration Page 6 of 47 - change of manufacturing process and methods; - change of manufacturer. Article 7: In the period of registration validity, the following changes to a registered drug product shall be subject to prior approval of MOH: - product name; - dosage; - labeling; - applicant; - manufacturer (provided that the site of manufacturer remains unchanged); - shape or colour of product, provided that the changes will not impose any impact to quality specifications and analytical methods of the product; - change or for more indications; - change or for more contra-indications; - site of manufacturer (provided that the manufacturer remains unchanged); - drug shelf-life; - presentation of product label; - change or for more packing sizes Application dossiers for the any of changes or additions specified in this Article shall include the following: - forms 1-DKT and 9A-DKT (for domestic drug products) or 9B-DKT (for imported drug product), or 9C-DKT for change of applicant (01 original copy) - documents related to the proposed changes or additions (01 original copy) For imported drug products, in applying for change of product name, the Free Sale Certificate in the country of manufacture for the product under new name must be submitted; applying for change of the site of factory, a GMP certificate for the factory at new location must be submitted; applying for change of name of manufacturer, a GMP certificate issued to the manufacturer under the new name. The aforesaid certificates (FSC, GMP) must be issued by Regulation on Drug Registration Page 7 of 47 the national competent authority in the country of manufacture. Article 8: - The registration is valid for 5 years from the date of issuance. The Ministry of Health shall have specific guidance to specific cases. The registration number given shall be printed on the drug label. - Six months prior to the expiry of the registration, for continuation of production and marketing of the drug product in Vietnam, the registration applicant shall apply for the re-registration. Applications for re-registration shall only be acceptable if being submitted not later than 6 months after the registration expiry. Submissions for re-registration that are made later than 6 months after the registration expiry follow requirements as new applications. - Application dossiers for re-registration is specified in Article 15, Chapter II, (for domestic drug products), Article 19, Chapter III (for imported drug products), Article 22, Chapter IV (for drug products under-licence) of this Regulation. Article 9: Requirements on stability studies and registration of shelf-life: 9.1. Stability of drug product: - All drug products shall be stored in such storage conditions as required by the manufactures that are given based on stability studies; - Reports of stability studies shall specifically indicates: conditions for storage of product sample (temperature, humidity, etc), package, methods of study, results of studies in all indicators conducted on at least three different batches, a conclusion of stability of the studied drug product. - Results of accelerated stability studies shall only be valid for prediction of drug shelf-life for new application for registration. For products under-licence: if report of normal stability studies conducted on the batches produced in Vietnam is not available, reports of stability studies conducted by the foreign licence holder can be used for registration purpose. During port-marketing period, the manufacturer shall monitor the stability of the drug product in normal conditions confirm the predicted product stability. Regulation on Drug Registration Page 8 of 47 Reports of normal stability studies shall be submitted as part of application dossier for re-registration. - For imported drug products that have been marketed for a period equivalent to or longer than the predicted shelf-life, report of normal stability studies shall be submitted as part of application for registration in Vietnam. 9.2. Shelf-life of drug product: - The product shelf-life shall be established basing on proper stability studies. The shelf-life of a drug product shall not be longer than the shelf-life obtained in stability studies. - Heads of applicant companies shall be responsible for the quality of drug products during the period of registered shelf-life. Article 10: Domestic registration applicants shall submit applications to its direct managing authorities (provincial departments of health, department of health of other ministries) for certification of legal status and manufacturing conditions with their opinions as request for registration approval of the Ministry of Health (with exception for the drug products included in Appendix 1). The direct managing authorities shall have their certification and opinions on the application of the applicants not later than 7 days from the date of receipt of proper application. The applications shall the then be submitted to the Ministry of Health for assessment and registration. Application dossiers of the members of VINAPHARM, of 100% foreign-invested manufacturers shall be signed and stamped by director of the manufacturers and then submitted to the Ministry of Health (with exception for the drug products included in Appendix 1). The MOH shall, after receiving a complete application dossier, have feedback to the applicant in 3 months for domestic drug product, and 12 months for foreign drug product at maximum. For the drug products included in the Appendix 1, the application dossiers shall be submitted to the provincial department of health of the Regulation on Drug Registration Page 9 of 47 respective province where the production takes place for assessment. Those applications that have passed assessment of the provincial department of health shall be listed (with accurate product names and compositions) and sent as an attachment to an official request to the Ministry of Health for approval and registration grant. Registration applicants after having drug product registered, shall be obliged to send the quality specifications of their registered products to the National Institute of Drug Quality control, the Sub-institute of Drug Quality Control and provincial drug quality control centers. Article 11: Registration applicants shall pay a fee as required by current regulations. Chapter II Application Dossiers for Registration of Domestic Drug Products Article 12: 12.1. Application dossier for registration of a medicinal starting material shall contain: - Cover page (form 1- DKT) - List of contents (form 2- DKT) - Application (form 3- DKT) - Manufacturing process (fully detailed) - Quality specifications and analytical methods (fully detailed ) - Certificate of analysis of the samples submitted for registration: must be released by either of the following institutions: National Institute or Sub-institute of Drug Quality Control or by the manufacturer of GMP standard; GLP standard Laboratories. - Report of stability studies of the material; - Labeling samples (as designed or attached to Form 7- DKT); - Samples: 1 sachets (sufficient for three analysis). Regulation on Drug Registration Page 10 of 47 12.2. Application dossier for registration of a domestic new medicinal starting material shall contain, in addition to those required in 12.1 of this Article, the following: - study report on toxicology; - study report on experimental pharmacology - study report on clinical pharmacology Article 13: 13.1. Application dossiers for registration of western drug product shall contain: - Covering page (from 1- DKT) - List of contents (from 2-DKT) - Application (from 4- DKT) - Summary of product characteristics (form 6- DKT); - Manufacturing process (fully detailed); - Quality specifications and analytical methods (fully detailed); - Certificate of analysis of the samples submitted for registration: must be released by either of the following institutions: National Institute or Sub-institute of Drug Quality Control or by the manufacturer of GMP standard; GLP standard Laboratories. - Reports of stability studies; - Labeling samples: (as designed or attached to Form 7- DKT); - Product samples: 1 packing units of the packing sizes applied for registration. 13.2. Application dossiers for a new western drug product shall contain, in addition to those required in 13.1 of this Article, the following: - Study report on toxicology (acute toxicity, sub-chronic toxicity, chronic toxicity, molecular toxicity, etc.); - Study report on experimental pharmacology; - Study report on pharmacokinetics and bio-availability; - Study report on clinical pharmacology； - Minute of meeting of appropriate ministerial scientific committee for Regulation on Drug Registration Page 11 of 47 assessment and acceptance. Article 14: 14.1. Application dossiers for registration of ancient medicines originated from medicinal plants, medicines originated from medicinal plants with known indications, the medicines that have been registered with the Ministry of Health, shall contain: - Cover page (form 1- DKT) - List of contents (from 2- DKT) - Application (form 4A-DKT) - Summary of product characteristics (Form 6); - Manufacturing process (fully detailed); - Quality specifications and analytical methods; - Certificate of analysis of the samples submitted for registration must be released by eit