Circular No. 16/2011/TT-BYT stipulates the principles for producing medicines from medicinal materials and the implementation timeline for Good Manufacturing Practice (GMP) standards for medicine production facilities using medicinal materials.

CIRCULAR

Specifies the principles for producing medicines from medicinal materials and the implementation timeline for Good Manufacturing Practice (GMP) principles and standards for medicine production facilities using medicinal materials.

Specifies the principles for producing medicines from medicinal materials and the implementation timeline for Good Manufacturing Practice (GMP) principles and standards for medicine production facilities using medicinal materials.

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Pursuant to the Medicine Law No. 34/2005/QH11 dated June 14, 2005;

Pursuant to Decree No. 79/2006/NĐ-CP dated August 9, 2006 of the Government detailing the implementation of certain provisions of the Medicine Law;

Based on Decree No. 188/2007/NĐ-CP dated December 27, 2007 of the Government stipulating the functions, tasks, powers, and organizational structure of the Ministry of Health;

Based on Resolution No. 62/NQ-CP dated December 17, 2010 of the Government regarding simplification of administrative procedures within the scope of management functions of the Ministry of Health;

Considering the actual situation in implementing the GMP principles and standards at medicine production facilities using medicinal materials based on recommendations by the World Health Organization;

The Ministry of Health hereby stipulates the principles for producing medicines from medicinal materials and the implementation timeline for Good Manufacturing Practice (GMP) principles and standards for medicine production facilities using medicinal materials as follows:

PART I

GENERAL PROVISIONS

Article 1. Scope of Regulation

Article 1. This Circular stipulates the principles for producing medicines from medicinal materials and the implementation timeline for Good Manufacturing Practice (GMP) principles and standards for medicine production facilities using medicinal materials.

Article 2. This Circular guides the dossier and procedures for assessing conditions for producing medicines from medicinal materials in medicine production facilities using medicinal materials.

Article 2. Explanation of terms

In this Circular, the following terms are understood as follows:

1. Medicine production facility using medicinal materials includes enterprises, business households operating under the Enterprise Law to produce medicines from medicinal materials or cooperatives and other entities engaged in activities related to the production of medicines from medicinal materials (referred to collectively as the facility in this Circular).

2. Medicines from medicinal materials are medicines produced from natural raw materials derived from animals, plants, or minerals.

Medicines with purified active ingredients extracted from medicinal materials, or medicines combining medicinal materials with synthetic chemical substances, are not considered medicines from medicinal materials.

3. Traditional Chinese medicine is a type of medicine from medicinal materials prepared according to the theories and methods of traditional Eastern medicine.

Chapter II

PRINCIPLES FOR PRODUCING MEDICINES FROM MEDICINAL MATERIALS

Article 3. Quality requirements for medicinal materials

Clause 1. All medicinal materials used in the production of medicines for human consumption must be quality tested; only those meeting quality standards and complying with relevant legal regulations may be used in production, compounding, and circulation.

Clause 2. Medicinal materials used for producing medicines must be supplied by entities possessing the necessary conditions for pharmaceutical business operations.

Point a. Purchasing medicinal materials from domestic cultivation sources must be done through contracts with organizations or individuals responsible for cultivating medicinal materials, which must include provisions ensuring the quality of the medicinal materials in accordance with regulations.

Point b. Production facilities must establish and retain records containing information about the source of supply, origin, harvesting, processing, and storage methods of medicinal materials used in production.

Clause 3. Quality control of medicinal materials and raw materials

Point a. All medicinal materials and initial raw materials used in the production process must meet quality standards. Facilities must have sufficient qualified personnel and equipment to carry out sampling, testing, and inspection of medicinal materials, intermediate products, semi-finished products, and finished products.

Point b. Reference samples of medicinal materials must be available for comparative testing: visual inspection, microscopic examination, and various chemical methods. Sampling of medicinal materials, intermediate products, semi-finished products, and finished products must be conducted according to approved procedures and must be performed by qualified and experienced personnel.

Point c. Documentation must be maintained to prove that all required sampling, testing, and inspection procedures have been carried out according to the procedures, and any deviations from the procedures must be fully recorded in the documentation.

Point d. Testing and inspection results for medicinal materials, raw materials, intermediate products, semi-finished products, and finished products must be recorded according to standards. Sufficient quantities of retained samples of medicinal materials, raw materials, semi-finished products, and finished products must be kept for each production batch.

Article 4. Provisions on personnel and training

1. The facility must have sufficient staff with appropriate qualifications to perform tasks within the scope of responsibilities of a manufacturer. Individual responsibilities must be clearly defined, understood by relevant individuals, and recorded in the job descriptions of the facility.

2. Personnel

a) The facility must have sufficient staff with appropriate qualifications and experience for production departments and commensurate with the scale of production at the facility. There must be a clear distinction between personnel in production, quality testing, and storage departments.

b) Staff must be trained professionally and with practical experience in drug production and drugs derived from medicinal materials.

c) Heads of production, quality control, and storage departments must possess knowledge and expertise in pharmacy and be professionally trained in medicinal materials.

3. Training

a) Production facilities must organize training according to a written program for all employees involved in production, quality control, and storage departments (including technical, maintenance, and cleaning staff) and other employees if necessary.

b) The facility must have an approved annual training program by authorized personnel at the facility and must maintain records of training.

Article 5. Provisions on Premises and Equipment

1. The premises of the facility must be located, designed, constructed, repaired, and maintained appropriately for production operations and commensurate with the scale of production at the facility.

2. Storage Areas

a) Storage areas must be spacious enough, commensurate with the scale of production, and properly segregated and isolated for raw materials, packaging materials, intermediate products, semi-finished products, finished products, special reserve products, products permitted for release, rejected, returned, or recalled products.

b) Storage areas must be designed or adjusted to ensure good storage conditions, prevent the entry of insects, rodents, and other animals, and prevent the spread of microorganisms into medicinal materials. Storage areas must be clean, dry, well-lit, and maintained at temperatures suitable for the stored items or as directed by the manufacturer. Adequate humidity and temperature monitoring equipment must be available, and daily monitoring records must be kept.

c) Special storage areas must be designated for substances requiring special storage conditions such as solvents, flammable and explosive materials, toxic substances, and similar materials.

d) Medicinal materials must be stored in separate areas, ensuring ventilation, moisture control, systematic arrangement, and labeling. Before being warehoused, medicinal materials must be visually inspected and tested for moisture content and related criteria. Records of inventory and periodic inspections must be maintained, and the process of material inflow, outflow, and stock must be documented. For the storage of extracts, concentrated extracts, or other preparations, suitable conditions regarding humidity, temperature, and light must be followed and monitored throughout the storage period.

đ) A tracking label system must be established and applied to monitor the status of raw materials, semi-finished products, and finished products, including different labels for special reserves, acceptance, and rejection, containing necessary information such as material name, batch number, test number, date of release/rejection or retest date/expiry date. Rejected medicinal materials must be clearly labeled and stored separately from accepted materials. Only those responsible for quality control may label the initial material status.

3. Pre-treatment/Processing and Manufacturing Areas for Medicinal Materials

a) Separate areas must be provided for the processing, pre-treatment, and manufacturing of medicinal materials, which must be distinct from other pharmaceutical production areas. Pre-treatment areas for medicinal materials include purification, removal of impurities, soil, unused parts; washing; cutting; drying, and processing crude medicinal materials (washing area, drying yard or drying room according to the requirements and scale of the facility).

b) Pre-treatment and processing areas for medicinal materials must be easy to clean, well-ventilated, safe, and operationally convenient, equipped with a minimum standard potable water supply for processing medicinal materials to meet hygiene standards.

4. Production Areas

a) The factory must be located in a suitable position, free from contamination, designed and constructed to facilitate convenient operation, maintenance, and cleaning, and protected from adverse weather effects. The factory must be designed and arranged with production rooms to ensure unidirectional flow principles for materials, personnel, products, and waste to prevent product mixing and/or cross-contamination or when dust-producing operations occur.

b) Production factories must be constructed, maintained, and protected against the entry and nesting of insects, rodents, and other animals.

c) The factory must have a fully designed and installed lighting system to ensure accurate work performance. It must be kept neat, clean, well-maintained, and sanitized according to detailed written procedures, and sanitation records must be kept for each production batch.

5. Quality Control Areas

a) Testing and quality control areas for drugs must be separated from production areas. Quality control rooms must be designed to accommodate activities conducted there and must have sufficient space to avoid confusion, cross-contamination, and to store samples, standards, solvents, reagents, and testing records.

b) Biological and microbiological testing areas must be separate and must have their own air handling equipment and other devices.

6. Auxiliary Systems

a) Air Handling System

Encourages investment in installing air treatment systems or separate air conditioning for production areas such as manufacturing, testing, storage, microbiological testing areas, sensitive substance production areas, and highly toxic substance production areas.

b) Water treatment system

Depending on the requirements of each type of pharmaceutical preparation, the water used for production purposes must meet the minimum standard of potable water or must comply with appropriate water standards suitable for the specific requirements of each type of pharmaceutical preparation.

Encourages investment in building a water treatment system that meets the ultrapure water standard for drug production units. Annual sampling and quality inspection plans for production water sources must be implemented.

c) Wastewater, exhaust gas, and waste treatment system

The facility must have measures to treat wastewater, exhaust gases, and manage waste products appropriately during production, ensuring safety and hygiene.

Encourages investment in building a wastewater treatment system and waste management facilities suitable for the scale of production at the facility, ensuring safety and hygiene.

d) Fire prevention and firefighting system

The facility must be equipped with sufficient fire prevention and firefighting equipment and have approved fire prevention and firefighting plans by the fire prevention and firefighting authority; Firefighting equipment must always be maintained in effective condition.

7. Production Equipment

a) The manufacturing plant must be equipped with all necessary equipment suitable for producing permitted pharmaceutical products at the facility.

b) Production equipment must be designed, selected, manufactured, installed, and maintained appropriately to ensure ease of operation, safety, easy cleaning and maintenance; to prevent cross-contamination, dust accumulation, and adverse effects impacting product quality.

c) Scales and measuring devices must be calibrated according to regulations. Calibration and verification procedures must be fully conducted, and calibration results must be recorded and retained.

d) Procedures for cleaning and maintaining equipment and tools must be established and ensured to be fully adhered to.

đ) Defective machines and equipment not in use must be removed from the production area and inspected for quality. If removal is not possible, they must be marked or labeled clearly as defective to prevent accidental use.

8. Weighing Area

Initial raw material weighing must be carried out in a dedicated weighing area designed for this purpose. This area may be located within the storage or production area.

9. Sanitation Area

Personal hygiene and rest areas must be separated from production or testing areas. Changing rooms, washing facilities must be easily accessible and suitable for the number of users. Bathrooms must not directly connect to production and storage areas.

Article 6. Sanitation and Hygiene Conditions

1. The facility must implement principles to ensure factory sanitation and personal hygiene throughout the drug production process, including factory cleaning, personal hygiene, machine and equipment cleaning, raw material and packaging material hygiene, and packaging material hygiene.

2. Sanitation Standards

The facility must establish and issue standards for hygiene inspections during production; work attire standards; methods for checking employee health conditions; handwashing and disinfection procedures.

3. Factory Sanitation

a) The facility must develop and implement appropriate factory and equipment cleaning procedures based on the requirements of each type of pharmaceutical preparation. These procedures must be reviewed periodically and approved by authorized personnel at the facility.

b) Measures must be taken to regularly handle production waste to maintain hygiene in this area; waste containers must be clearly marked, emptied, and cleaned regularly, at least once daily.

4. Personal Hygiene

a) Employees working in production departments must be trained and instructed on practices to ensure factory, equipment, tool, and personal hygiene conditions.

b) The facility must have measures to ensure employees adhere to personal hygiene regulations suitable for production requirements and the nature of each type of pharmaceutical preparation.

c) Machine operators must not come into direct contact with initial raw materials, direct packaging materials, intermediate products, and semi-finished products with their bare hands.

d) Employees must be provided with appropriate personal protective equipment such as gloves, hats, protective clothing, masks, and suitable footwear for each production stage. Measures must be taken to protect employees from direct contact with harmful substances and allergenic medicinal materials.

đ) Smoking, eating, keeping fresh plants, food, beverages, medicines, and personal items is prohibited in production areas, quality control rooms, storage areas, or other areas that could adversely affect product quality.

Article 7. Provisions on Documentation and Records

1. The entity must establish a system of documentation and records to determine standards and procedures for all raw materials, finished products, and production methods as well as quality control; to ensure that all employees involved in production understand and properly perform their assigned tasks; to ensure that authorized persons have all necessary information when deciding to release a batch of medicine to the market; and to ensure that there are evidences in the records that can be retrieved and provided to inspectors for investigation. Documentation and records must contain sufficient data for evaluation, review, and statistical analysis.

2. Labels

a) Labels used for packaging, machines, equipment, or facilities must be clear, not ambiguous, and follow a common standardized model of the entity in accordance with regulations on labeling medicines. In addition to the text on the label, colors may be used to indicate the status of raw materials, machines, and equipment (for example, stored separately, accepted, rejected, or clean).

b) All finished medicines must be identified and labeled in accordance with current regulations on labeling medicines.

c) For reference standards, labels and/or accompanying documents must clearly state the potency or concentration, date of manufacture, expiration date, first opening date of the package, storage conditions, and control number if applicable.

3. Documentation on Quality Standards

Initial raw materials, intermediate products, semi-finished products, and finished products must have complete standards and analytical testing methods. Initial raw materials must meet the standards of the Vietnamese Pharmacopoeia, internal standards, and quality and hygiene regulations as stipulated by the Ministry of Health.

a) Standards for initial raw materials and packaging materials

Standards for initial raw materials, primary packaging, and printed packaging, if appropriate, must include descriptions of the materials, which must contain the following information:

- Name (if possible, including the INN name) and internal code number. For medicinal herbs, minimum information such as name and origin (medicinal herb name, scientific name, part used), sensory description must be included.

- Reference to the monograph of the Pharmacopoeia, if applicable.

- Requirements for qualitative and quantitative identification, permissible limits.

Depending on the requirements of the entity, standards may also include other information such as: supplier and original manufacturer of raw materials, sample of printed packaging, sampling and testing instructions, or reference to the implementation procedure, storage conditions, precautions, maximum storage period before retesting, expiration date.

Direct packaging materials for medicines must meet the standards specified in the Vietnamese Pharmacopoeia and must be compatible with the raw materials and/or products contained within them. Raw materials need to be tested for quality standards, defects, and the accuracy of identification marks.

Documentation describing the testing procedures must specify the frequency required for retesting each initial raw material, depending on their shelf life.

b) Standards for intermediate and semi-finished products

There must be documentation on standards for intermediate and semi-finished products. If these products are purchased or sent out, or if data from intermediate products are used to evaluate finished products, the standards must be similar to those of initial raw materials or finished products, if appropriate.

c) Finished Product Standards

Finished product standards must include key information such as: Product name and reference code if applicable; Active ingredient name; Formula or formula reference; Description of dosage form and detailed packaging; Sampling and testing instructions, or reference to the implementation procedure; Qualitative and quantitative requirements, permissible limits; Storage conditions and precautions if applicable; Expiration date.

Finished product standards must include tests for active ingredients that can be qualitatively and quantitatively determined in finished product quality control tests. Tests to determine the permissible limits of residual substances used for preservation, cleaning (if applicable), and excipients involved in the drug processing must be included.

Additionally, there must be tests for other relevant criteria according to the specific requirements of each dosage form, such as: External appearance like color, taste, size, and texture; Uniformity of weight, disintegration time, hardness (for tablets), clarity, viscosity (for solutions), homogeneity (for ointments, creams); Loss on drying or water content; Microbial contamination, etc.

4. Original Formula Documentation

The entity must develop an officially approved original formula for each product and each batch size. The original formula must include the following information: Product name, with a reference code related to the standard; Description of dosage form, strength, and batch size; List of initial raw materials used (INN name if applicable), quantity of each substance, described by name and a consistent reference symbol for that type of raw material (must specify which substance will be lost during processing); Announcement of expected finished product yield and permissible limits, and intermediate product yield, if applicable; Indication of manufacturing location and main equipment used; Methods, or method references, used to prepare and operate important machinery and equipment, such as cleaning (especially after changing products), installation, calibration, sterilization, usage; Detailed manufacturing instructions step-by-step (for example: raw material inspection, preliminary processing, sequence of adding raw materials, mixing time, temperature); Instructions for in-process inspections and corresponding limits; If necessary, storage regulations for the product, including packaging, labels, and special storage conditions; particular precautions needed during production.

5. Batch Manufacturing Record Documentation

a) Must establish a record for each production batch, specifying: Name, concentration, content of the product; Date of production; Batch number, lot number; Full formula of the batch/lot; All SOPs used and recording each stage carried out, all main equipment used, all samples, results of inspections during production, environmental condition inspection results, equipment inspection before starting and during production, packaging, and final label sample retention on the final packaging.

b) Must retain a processing record for each production batch. The record must be based on relevant sections of the original standard that has been approved. The method of preparing the record must be designed to avoid errors. (Photocopies should be made or computer programs that have been validated should be used. Manual copying of approved documents should be avoided).

c) Must establish processing guidelines listing different operations performed on medicinal materials, such as drying, cutting, and grinding, also specifying the necessary temperature and time for drying, and the method used to check particle size or sub-particle size.

d) Must provide guidance on screening or other methods used to remove foreign contaminants. Any process, such as steam sterilization, used to reduce microbial contamination, along with the method to determine the level of these contaminations, must be detailed.

For the production of high-concentration preparations from medicinal materials, the guidelines must specify the solvent or medium used, the time and temperature required throughout the extraction process, and any concentration methods.

The guidelines must clearly state the steps in the mixing and adjustment process to ensure the active pharmaceutical ingredient content and homogeneity of the batch after mixing, and regulations regarding recording parameters during the mixing process.

Measures must be established to dispose of medicinal materials after processing if they do not meet quality standards.

e) For the finished product manufacturing phase, there must be records for all raw materials used; all standard operating procedures; each batch and/or each processing and distribution lot; all equipment, including operation, cleaning, maintenance, and validation; and records for cleaning, maintenance, and environmental control of the production area.

All records must indicate the date and be signed by the person responsible for performing the work; for important operations, signatures of supervisors must also be included and kept at the workplace throughout the operational period. Records must be retained and available for inspection for at least two years after the expiration date of the drug batch.

6. Procedures and Record Keeping

There must be standard operating procedures guiding production, equipment, and tool sanitation and maintenance, specifying: assignment of sanitation responsibilities; schedule for determining sanitation and equipment maintenance; method of implementation; equipment and materials used; guidelines for storing sanitized equipment free from contamination; equipment sanitation status control before use. These procedures must be fully adhered to.

Article 8. Provisions on production and control during the production process

1. The facility must ensure that all production operations are carried out according to the procedures registered in the drug production and circulation permit.

2. Raw materials

a) Initial raw materials

All initial raw materials or crude materials used in the production process must meet quality standards and must be tested and found to be of acceptable quality. The facility must establish records documenting the receipt, dispatch, and inventory status of raw materials and semi-finished products.

Handling of raw materials and products, such as receiving and storing separately, sampling, storage, labeling, distribution, processing, packaging, and distribution, must be conducted according to established procedures or written guidelines and recorded if necessary.

For raw materials of animal origin, detailed information about the supplier, origin, and method of production must be recorded in the file. These materials need to be stored under controlled conditions and clearly marked with their expiration date or retest date.

Raw materials and products that are discarded must be clearly labeled to indicate their condition and stored separately in restricted areas. Discarded raw materials must be safely stored and kept separate from accepted raw materials.

The facility must develop and implement a stock rotation program based on the principle of "first-expired-first-out" (FEFO) and "first-in-first-out" (FIFO).

b) Packaged raw materials

Purchasing, managing, and testing directly packaged raw materials and pre-printed packaging must be conducted as for initial raw materials.

Packaging materials and pre-printed packaging must be stored in a restricted access area and distributed under strict supervision.

c) Intermediate and semi-finished products

Intermediate and semi-finished products awaiting packaging must be stored separately until they are inspected for quality before proceeding to the next stage.

All dispatches of intermediate and semi-finished products, including additional dispatches required for production, must be accompanied by complete documentation.

If components/raw materials are transferred to new packaging, the new packaging must be identified with a label containing: the name or code of the component/raw material, the receipt number or control code, and the quantity in the new packaging. Distribution/supplementary dispatches must be fully monitored, and each component/raw material must be checked by a second person to ensure that:

- The component/raw material has been authorized for dispatch for use by the quality control department.

- The quantity matches the dispatch order.

- The containers have been correctly identified.

d) Sampling provisions

There are provisions for labeling to clearly identify the boxes and packaging of raw materials sampled. Each sample taken must include the following information: the sampler's name, the amount of the sample collected, the container size, and the sampling date.

Initial raw materials must be stored separately until they are accepted and approved for use.

3. Production processes

a) Batch numbering system

There must be a system describing the details of batch numbering, including the identification of initial raw materials, packaging materials, intermediate products, semi-finished products, and finished products.

Batch numbering must be recorded immediately and must include the following information: the date of issuance, product identification, and batch size.

b) Weighing and dispensing

The weighing area must be equipped to prevent cross-contamination and must be physically separated from other rooms by walls or partitions.

Before weighing and dispensing, environmental conditions regarding hygiene, temperature, and humidity must be checked to ensure that the weighing and dispensing area is clean and that weighing and dispensing are performed accurately. Sterile raw materials must be weighed and dispensed in a sterile area. Staff must wear appropriate attire.

Careful measures must be taken to prevent cross-contamination during weighing. Procedures for managing the dispensing of initial raw materials, intermediate products, and semi-finished products must be established.

c) Production

The number of production staff must be adequate, and appropriate measures must be taken to monitor all processing operations. Staff must wear appropriate attire to perform processing operations.

The environment and production conditions must comply with regulations. All processing equipment must be inspected before use. Scales and measuring instruments must be calibrated and have the appropriate accuracy for the raw materials being weighed or measured.

A preliminary processing and handling procedure for medicinal materials must be established. When handling medicinal materials, care must be taken to avoid affecting their quality.

During processing, all raw materials, packaging containers for semi-finished products, precision machinery and equipment, and if applicable, packaging rooms and lines in use must be labeled or marked with the name of the product or raw material being processed, concentration (if applicable), and batch number. All inappropriate labels and markings present before processing must be completely removed.

Tablet presses without a closed environment must be placed in a separate area. Weight and hardness tests of tablets must be conducted during tablet pressing.

For capsule production, capsule weighing must be conducted throughout the encapsulation process. Tablets or capsules taken directly from the tablet press or encapsulation section for testing or other purposes must be collected and properly disposed of.

Empty capsule shells must be stored under conditions that prevent drying, cracking, or moisture damage.

Ink used for printing tablets and capsules must be food-grade dye and considered a production material.

Liquids, creams, and ointments must be produced using methods and conditions that prevent bacterial and other types of contamination. Production and transportation of liquids, creams, and powders must be conducted in a closed system.

d) Intermediate and finished products

There must be a system for separate storage and dispatch of semi-finished and finished products, including clearly identifying the status of the product (storage, dispatch, removal). A system and process for handling non-conforming products and returned products must be established.

d) Control during production

All inspections, controls, and recording of all test results during production and environmental monitoring must be conducted according to the production procedures and batch records.

4. Labeling, packaging, and distribution

a) Packaging

Standards for direct packaging materials and pre-printed packaging must be established. Standard Operating Procedures (SOPs) for receiving, sampling, and testing packaging material must be developed.

b) Labeling and packaging activities

Labeling and packaging activities must be physically separated to prevent confusion between products and packaging materials. Samples of labels and printed packaging materials must be kept in batch records. Separate and secure storage areas for finished products awaiting dispatch must be provided.

c) Storage and distribution

SOPs for storing dispatched finished products in the shipping area must be established. Records allowing quick identification of all customers who have purchased finished products from a specific batch/lot, specifying the time of dispatch, quantity, packaging specifications, and shipping details for each batch of products to customers, must be maintained.

Records of storage time, temperature, and other storage conditions before distribution must be stored.

5. Sanitation in production

Measures must be taken to control the use of insecticides to prevent product contamination. Wastewater, waste, and rejected raw materials must be controlled and/or treated safely and hygienically. The movement of personnel in restricted access areas must be regulated.

Article 9. Quality Testing Provisions

1. Pharmaceutical manufacturing facilities using medicinal herbs must conduct testing on each batch of drugs, and only batches meeting registered standards may be dispatched.

2. Pharmaceutical manufacturing facilities using medicinal herbs must establish a quality control and testing department commensurate with their production scale. The quality control department must be independent and under the management of a person with appropriate expertise and experience, capable of managing one or more laboratories. Adequate resources must be available to ensure that all quality control measures are effectively and reliably implemented.

3. For pharmaceutical manufacturing facilities that have not established a drug testing department or have established such a department but cannot test all quality criteria, samples must be sent and contracts for testing must be signed with units having the necessary conditions and functions to perform testing for each batch of drugs produced at the facility or to test the quality criteria not performed at the facility. Test reports must be kept in the batch records of dispatched drugs.

4. Quality control personnel

Quality control personnel must have specialized knowledge about herbal-based pharmaceutical products to conduct qualitative tests, detect counterfeits, presence of mold or insects, and uniformity of herb batches. The quality control department must have adequately trained, qualified, and experienced staff to complete assigned tasks.

5. Equipment

a) The quality control department or laboratory must be designed appropriately, providing sufficient space for specialized equipment, documentation, and workspaces for personnel.

b) The quality control laboratory must be equipped with suitable machines, devices, and tools for sampling, analysis, calibration, and data processing. Analytical equipment must be compatible with testing methods and meet the quality control requirements of the unit. The physical chemistry laboratory must be equipped with instruments to check chemical parameters (drying ovens, furnaces, dissolution testers, thin-layer chromatography systems, incubators, etc.) and production process monitoring equipment. For expensive analytical equipment like gas chromatography or difficult tests like sterility testing, these can be outsourced. Test results must be systematically recorded for long-term tracking.

6. Records and Documentation

a) The laboratory must maintain analyst notebooks, analytical records, test reports, and analytical forms.

Analyst notebooks must record results, calculations, data, and relevant observations regarding sample analysis. Pages must be numbered, and pencils must not be used for writing, nor should entries be erased or overwritten.

b) Analytical records must contain full information about the sample, testing method, and analysis results, pre-printed with minimum information such as: Sample name, origin/place of manufacture, reference code if applicable; Batch number, expiration date, analysis requirements (number, date, and content); Date of receipt, receiver; Quality standards and testing methods; Sample condition upon receipt and prior to analysis; Analysis results (including calculations). Analytical records must be kept in the testing file along with analysis results. Analytical forms must be signed by the tester and supervisor.

c) All necessary quality standards for testing work must be updated and retained, including: Vietnamese Pharmacopoeia and foreign Pharmacopoeias, including appendices, supplements, and revisions; Quality standards not included in the Pharmacopoeia, for drugs tested based on manufacturer standards. Testing methods not included in the Pharmacopoeia developed and issued by the testing laboratory.

7. Stability Monitoring

Facilities must establish procedures and maintain stability monitoring records for drugs they produce. Stability monitoring records for drugs must be retained.

Article 10. Provisions on complaints and product recalls at the facility

1. Complaints about products

The facility must establish written procedures for handling all issues related to complaints regarding products and designate individuals responsible for receiving, forwarding, reviewing, and evaluating complaints about products produced by the facility. The handling of product complaints must be recorded in writing and retained for the duration of the shelf life of the batch of drugs being complained about.

2. Returned products

The facility must establish records to track and develop written procedures for accepting and inspecting returned products. Records of returned products must include the following contents: name and quantity of the product, dosage form, batch number, reason for return, quality of the returned product, date of return. Returned products must be clearly identified and stored in a segregated area.

3. Product recalls

The facility must establish written procedures for handling product recalls and specify the authorized person to decide on recalling a product. Records and reports on product recalls, including the results of the recall and any containment actions, must be established and retained. Recalled products must be stored in a secure location to prevent their reintroduction into circulation and use without prior investigation and evaluation.

Article 11. Provisions on self-inspection activities at the facility

The facility must establish a plan for self-inspection activities and identify suitable members of the inspection team. Self-inspection activities must be documented and a self-inspection report prepared to take appropriate corrective actions.

Chapter III

RECORDS AND PROCEDURES FOR REVIEWING PRODUCTION CONDITIONS OF DRUGS FROM PHARMACEUTICAL RAW MATERIALS

Article 12. Application dossier for reviewing production conditions of drugs from pharmaceutical raw materials and issuing a Certificate of Compliance for Drug Business Conditions

1. The application dossier for reviewing production conditions of drugs from pharmaceutical raw materials and issuing a Certificate of Compliance for Drug Business Conditions includes:

a) An application for review and issuance of a Certificate of Compliance for Drug Business Conditions (Form No. 1);

b) A copy of the Pharmaceutical Practice Certificate of the professional manager in pharmacy corresponding to the form of drug business organization; a copy of the Business Registration Certificate.

c) A list of personnel, specialized equipment, technical facilities

- A list of personnel and description of functions and responsibilities (Form No. 3)

- Organizational structure diagram directly related to the drug production process.

- List of equipment, machinery, technical facilities serving production, testing, and storage of drugs

- Layout diagram of major production equipment, machines, and tools

- Overall layout diagram of the production floor and movement directions of staff, raw materials, packaging.

- Storage warehouse layout diagram

2. The application dossier for expanding the scope of business and issuing a Certificate of Compliance for Drug Business Conditions includes:

a) An application for review and expansion of the scope of drug business (Form No. 2);

b) A copy of the previously issued Certificate of Compliance for Drug Business Conditions.

3. The application dossier for extending the validity period of the Certificate of Compliance for Drug Business Conditions as stipulated in Clause 3, Article 15 of this Circular.

The application for extending the validity period of the Certificate of Compliance for Drug Business Conditions must contain the following information: name and address of the facility; name and surname of the professional manager in pharmacy, pharmaceutical practice certificate number; type of drug formulation requested for extension (specify the formulation type), certificate of compliance for drug business conditions number already issued, issue date and place of issue.

4. The facility must prepare one set of the application dossier for reviewing production conditions of drugs and issuing a certificate of compliance for drug production conditions and submit it to the Ministry of Health (Department of Medicine Administration) or the Provincial Department of Health according to the provisions of Article 14 of this Circular. The dossier must be securely bound into a volume with a cover page and arranged in the following order: Cover page (Form No. 4); Table of contents (Form No. 5); Subsequent pages must be arranged in accordance with the table of contents.

5. Copies in the dossier must be certified true copies in accordance with current regulations on certification or original copies certified by the director of the facility with a stamp of authentication, and the facility bears full responsibility under the law for the authenticity of the copies included in the dossier.

Article 13. Procedure for assessing production conditions of drugs from medicinal materials and issuing a certificate of qualification for drug business

1. Within twenty working days from the date of receiving a valid dossier, the Ministry of Health (Drug Administration Department) or the Provincial Health Departments must organize the establishment of an assessment team to assess the production conditions of drugs at the facility; if it is not possible to conduct the assessment within this period, they must provide a written response and specify the reasons within ten days from the date of receiving the dossier.

2. At the time of assessing the production conditions of drugs, the production facility must carry out production activities, quality control, and storage of drugs (for new facilities registering for the first time, production activities may be conducted on placebo samples for the assessment team to evaluate the production conditions of drugs according to the principles of producing drugs from medicinal materials as stipulated in Chapter II of this Circular).

3. The assessment team shall prepare an Assessment Record of Production Conditions of Drugs from Medicinal Materials according to Form No. 6. The Assessment Record shall be prepared in three copies, two copies retained by the organizing authority, and one copy retained by the facility. The Assessment Record must clearly state the conclusion regarding whether the conditions (production lines, dosage forms produced) have met, not met, or failed to meet the principles of producing drugs from medicinal materials as prescribed in this Circular. In cases where the facility disagrees with the opinions of the assessment team, all reservations of the facility must be clearly recorded in the Assessment Record.

4. If the production facility has met the principles of producing drugs as prescribed in Chapter II of this Circular, within twenty working days from the date of conducting the assessment of production conditions at the facility, the Ministry of Health or the Provincial Health Departments must issue a certificate of qualification for drug business to the facility; if not issued, a written response must be provided specifying the reasons.

5. If the production facility has not met or failed to meet the principles of producing drugs from medicinal materials, the reasons and corrective measures must be clearly recorded in the Assessment Record. Within sixty days from the date of the assessment, the facility must implement corrective measures as required by the assessment team and submit a report on corrective actions (accompanied by supporting documents) to the Drug Administration Department or the Provincial Health Departments. Based on the facility's report on corrective actions, within ten working days from the date of receiving the report, the Ministry of Health or the Provincial Health Departments must issue a certificate of qualification for drug business to the facility; if not issued, a written response must be provided specifying the reasons.

6. Ninety days before the expiration date of the certificate of qualification for drug business, the facilities must submit a dossier requesting reassessment of the production conditions of drugs from medicinal materials so that the Ministry of Health/Provincial Health Departments can schedule the assessment time.

7. The assessed facility is responsible for paying the assessment fee for production conditions of drugs from medicinal materials in accordance with current regulations on fees and charges of the Ministry of Finance.

Article 14. Authority to Issue, Supplement, Extend, Reissue, and Replace Certificates of Qualification for Drug Business

1. The authority to issue, supplement, extend, and reissue certificates of qualification for drug business for various types of drug businesses has been guided in Clause 3, Article 11 of the Medicine Law.

2. For the type of producing drugs from medicinal materials, the authority to issue, supplement, extend, and reissue certificates of qualification for drug business is defined as follows:

a) The Provincial Health Departments shall issue, supplement, extend, and reissue certificates of qualification for drug business for production facilities producing drugs from medicinal materials registered as individual businesses, cooperatives; enterprises only producing drugs for external use from medicinal materials; and facilities producing, processing, and packaging medicinal materials.

b) The Ministry of Health shall issue, supplement, extend, and reissue certificates of qualification for drug business for enterprises producing drugs from medicinal materials and other cases except those specified in point a, Clause 2 of this Article.

Chapter IV

IMPLEMENTATION TIMELINE FOR THE PRINCIPLES AND GOOD MANUFACTURING PRACTICE STANDARDS (GMP) FOR PRODUCTION FACILITIES OF DRUGS FROM MEDICINAL MATERIALS

Article 15. Implementation timeline for applying the principles and standards of "Good Manufacturing Practice for Medicinal Products" (GMP) to establishments producing medicines from medicinal materials.

1. From the date this Circular takes effect, new establishments producing medicines from medicinal materials, those expanding their pharmaceutical business scope, or those renewing their certificates of eligibility for pharmaceutical business operations must comply with the production principles set forth in Chapter II of this Circular.

2. Establishments producing medicines from medicinal materials that are currently permitted to operate but have not yet undergone production condition assessment pursuant to Decision No. 15/2008/QĐ-BYT dated April 21, 2008 of the Ministry of Health may continue operations until the expiration date of their certificates of eligibility for pharmaceutical business operations, but not later than December 31, 2012.

3. Establishments producing medicines from medicinal materials that have been assessed for production conditions pursuant to Decision No. 15/2008/QĐ-BYT dated April 21, 2008 of the Ministry of Health and granted certificates of eligibility for pharmaceutical business operations valid until December 31, 2010 shall be considered for extension or issuance of new certificates of eligibility for pharmaceutical business operations valid until December 31, 2013. The procedures for extending certificates of eligibility for pharmaceutical business operations are stipulated in Clause 3, Article 12 of this Circular.

4. As of January 1, 2014, establishments producing medicines from medicinal materials must meet the Good Manufacturing Practice (GMP-WHO) principles and standards recommended by the World Health Organization to be eligible for pharmaceutical business operations. In cases where establishments producing medicines from medicinal materials register for business operations without meeting the GMP-WHO principles and standards, they must adhere to the production principles specified in this Circular and will only be considered for permission to produce traditional medicines and must undergo re-assessment of production conditions every three years.

5. Based on the implementation timeline for the Good Manufacturing Practice principles and standards and the production principles for medicines from medicinal materials as prescribed in this Circular, the Drug Administration will guide establishments regarding the procedures for extending registration numbers for medicines from medicinal materials valid until December 31, 2010 for establishments producing medicines.

Chapter V

IMPLEMENTATION

Article 16. Transitional Provisions

1. Establishments producing medicines from medicinal materials that have been assessed for production conditions pursuant to Decision No. 15/2008/QĐ-BYT dated April 21, 2008 of the Ministry of Health and granted certificates of eligibility for pharmaceutical business operations valid after December 31, 2010 are permitted to continue operating until the expiration date of their certificates of eligibility for pharmaceutical business operations, but not later than December 31, 2013.

2. Prior to January 1, 2014, newly issued, supplemented, or renewed certificates of eligibility for pharmaceutical business operations for establishments producing medicines from medicinal materials that do not meet the Good Manufacturing Practice (GMP-WHO) principles and standards shall only be valid until December 31, 2013.

3. Within the period from January 1, 2011 to the date this Circular takes effect, establishments producing medicines from medicinal materials that have been granted certificates of eligibility for pharmaceutical business operations valid until December 31, 2010 may continue their pharmaceutical business activities in accordance with the conditions and business scope already approved in their certificates of eligibility for pharmaceutical business operations.

Article 17. Provisions on Reporting System

Pharmaceutical production facilities from medicinal materials must report to the Drug Administration of Vietnam under the Ministry of Health on their monthly pharmaceutical production situation via an electronic file according to Model No. 7 to the email address [email protected] before the 10th day of each month; submit a six-month report in writing (with an attached electronic file) before July 10th; and provide an annual report before January 10th of the following year.

Article 18. Effective Date

1. This Circular takes effect from June 8, 2011. The provision at point h, Clause 1, Article 1 of Decision No. 27/2007/QĐ-BYT dated April 19, 2007, issued by the Minister of Health regarding the implementation timeline for applying the "Good Manufacturing Practice" principles and standards and the "Good Storage Practice" principles is hereby abolished.

2. In the course of implementation, if there are difficulties or obstacles, units are requested to report to the Ministry of Health (Drug Administration) for consideration and guidance./.