Decision No. 15/2008/QD-BYT Issuing Temporary Provisions on Basic Principles for Producing Medicines from Herbal Materials until December 31, 2010

Pursuant to …;

Issuing Temporary Provisions on Basic Principles for Producing Medicines from Herbal Materials until December 31, 2010

THE MINISTER OF HEALTH

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

Pursuant to 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;

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;

Pursuant to Decision No. 108/2002/QĐ-TTg dated February 15, 2002 of the Prime Minister approving the "Strategy for the Development of the Pharmaceutical Industry until 2010";

Considering the actual situation in implementing the principle of "Good Manufacturing Practice for Medicinal Products" recommended by the World Health Organization at facilities producing and trading medicines from herbal materials;

Considering the proposal of the Director of the Drug Administration Department,

DECISION:

Article 1. Issued along with this Decision are Temporary Provisions on Basic Principles for Producing Medicines from Herbal Materials until December 31, 2010 (hereinafter referred to as the Provisions on Producing Medicines from Herbal Materials). These provisions are based on the principles and standards of "Good Manufacturing Practice for Medicinal Products" recommended by the World Health Organization.

Article 2. During the period before December 31, 2010, production facilities for medicines from herbal materials that comply with the principles set out in the Provisions on Producing Medicines from Herbal Materials will be eligible to operate. It is encouraged that production facilities for medicines from herbal materials implement the principles and standards of "Good Manufacturing Practice for Medicinal Products" recommended by the World Health Organization.

Article 3. The Director of the Drug Administration Department is tasked with developing and issuing a "List of Inspection Conditions for the Production of Medicines Originating from Herbal Materials" based on the Provisions on Producing Medicines from Herbal Materials, serving as a basis for self-inspection and inspection of production conditions for facilities producing medicines from herbal materials until December 31, 2010.

Article 4. This Decision shall take effect fifteen days after its publication in the Official Gazette.

Article 5. The Heads of the Ministry's Office, Inspectorate, Drug Administration Department, Heads of subordinate units under the Ministry, Directors of Provincial Health Services, Central City Health Services, and Health Departments are responsible for enforcing this Decision.

TEMPORARY PROVISIONS

Basic Principles for Producing Medicines from Herbal Materials until December 31, 2010

(Issued together with Decision No. 15/2008/QĐ-BYT dated April 21, 2008)

 

I. Definitions:

The definitions stated below apply to terms used in these temporary provisions based on the guidance of Good Manufacturing Practice for Medicinal Products recommended by the World Health Organization.

Medicines from Herbal Materials

Medicines from Herbal Materials are medicines produced from raw materials of natural origin from animals, plants, or minerals.

Batch

Lot

A defined quantity of starting material, packaging material, or product processed in a single operation or series of operations and having uniform characteristics. Sometimes it may be necessary to divide a lot into several sublots which are then combined to form a final uniform lot. In the case of terminal sterilization, the lot size is determined by the capacity of the autoclave. In continuous production, the lot corresponds to a defined portion of production with specific characteristics expected to be uniform. The lot size can be defined as a fixed quantity of product or a quantity of product produced within a fixed time period.

Lot Number

A clear combination of numbers and/or letters used to uniquely identify a lot, recorded on labels, lot records, corresponding test reports, etc...

Lot Record

All documentation related to the production of a semi-finished or finished product lot. They reflect the history of each product lot and situations related to the quality of the final product.

Semi-Finished Product

A product that has undergone all manufacturing processes except for packaging.

Calibration

A series of actions aimed at establishing, under specified conditions, a relationship between values obtained by a measuring device or system (especially scales), and control, or values represented by a measurement standard, compared to known corresponding values of a reference standard. Acceptable limits of measurement results must be established.

Clean Area

 

An area where measures are taken to control particulates and microorganisms, constructed and used in such a way as to reduce the introduction, generation, and retention of contaminants within the area.

Shipment (or Delivery Batch)

A quantity of pharmaceuticals produced by a manufacturer and supplied in one delivery (at one time) according to a specific request or order. A shipment may include one or more cartons or containers and may consist of products from one or more lots.

Contamination

Unwanted contamination of chemical or microbiological impurities, or foreign particles, introduced into a starting material or intermediate product during production, sampling, packaging, repackaging, storage, or transportation.

Critical Operation

An operation in the manufacturing process that can cause changes in the quality of medicinal products.

Cross-Contamination

The contamination of one starting material, intermediate product, or finished product with another starting material or product during production.

Finished Product

A complete dosage form that has undergone all manufacturing processes, including final packaging and labeling.

In-Process Control

Inspections carried out during production to monitor and, if necessary, adjust the process to ensure that the product meets predetermined standards. Environmental or equipment controls may also be considered part of in-process control.

Intermediate Product

A partially processed product that still requires further processing steps to become a semi-finished product.

Manufacturer

A company engaged in activities such as manufacturing, packaging, repackaging, labeling, and relabeling of pharmaceuticals.

A document or set of documents specifying the initial raw materials and their quantities, packaging materials, together with a description of the processes and points of caution for producing a defined quantity of finished product, as well as instructions on processing, including inspection during production.

Original batch record

A document or set of documents used as the original for a batch record (blank batch record).

Packaging

All operations, including bottling and labeling, to transform a semi-finished product into a finished product. Bottling a sterile product under sterile conditions, or a product that will be sterilized at a later stage, is generally not considered part of packaging.

Packaging material

Raw materials, including printed materials, used in the packaging of a pharmaceutical, excluding outer packaging for transportation. The packaging material referred to here is called primary or secondary packaging depending on whether they come into direct contact with the product.

 

Pharmaceutical products

An ingredient or product intended for human or veterinary use, presented in finished dosage form or as active substance for such dosage form, shall be subject to the provisions of the pharmaceutical laws of both the exporting and/or importing country.

Manufacturing

All operations related to the manufacture of a pharmaceutical, from receipt of raw materials through processing, packaging, repackaging, labeling, relabeling, until completion of the finished product.

Quality assurance

Quality assurance is a broad concept encompassing all issues affecting the quality of a product, either generally or specifically. It includes all plans designed to ensure that pharmaceutical products meet their intended use in terms of quality.

Quality Inspection

Quality control is a process involving sampling, standards, and testing, as well as organizational, documentation, and release procedures to ensure appropriate and necessary tests have been conducted, and raw materials are not released for use or products are not released for sale or supply unless they have been assessed as meeting quality requirements.

Quarantine

The physical separation, or by other effective means, of initial raw materials or packaging materials, intermediate products, semi-finished products, or finished products while awaiting a decision on release for sale, disposal, or recycling.

Comparison

The comparison between theoretical quantity and actual quantity.

Recovery

The reintroduction of a portion or all of a previous batch (or redistilled solvent or similar products) of acceptable quality into another batch at a specific stage in the manufacturing process. Recovery includes the removal of impurities from waste to obtain a pure substance or the restoration of previously used raw materials for reuse in another purpose.

Reprocessing

Bringing back the entire or a part of a batch/lot of pharmaceuticals being processed, intermediate product (final biological product before packaging), or semi-finished product of a single batch/lot to a previous stage in the approved manufacturing process due to non-compliance with predetermined quality standards.

Reprocessing may sometimes be necessary for biological products, in which case reprocessing must have been evaluated and approved beforehand in the marketing authorization.

Reconditioning

Bringing back the entire or a part of a batch/lot of pharmaceuticals being processed, intermediate product (final biological product before packaging), or semi-finished product of a single batch/lot to a different manufacturing process due to non-compliance with predetermined standards. Such reconditioning is an undesirable situation and is not pre-approved in the product's marketing authorization.

Closed system

Facilities ensuring complete separation in all aspects, including personnel and equipment movement, according to established, controlled, and closely monitored procedures. A closed system includes mechanical barriers as well as separate air handling systems, but does not necessarily need to be located in separate buildings.

Basic standard

A list of specific requirements that a product or raw material used or obtained during production must meet. Standards serve as a basis for assessing quality.

Standard Operating Procedure (SOP)

A written and approved procedure providing guidance for performing tasks, not necessarily specific to each product or raw material (e.g., machine operation, maintenance, cleaning; validation; facility cleaning and environmental monitoring; sampling and inspection). Some SOPs may be used to supplement product records and original batch records for specific products.

Initial raw material

A material of defined quality used in the manufacture of a pharmaceutical, but not packaging material.

Appraisal

An activity aimed at demonstrating that a process, procedure, machinery, raw material, activity, or system actually produces the desired results.

II. Principles

1. Pharmaceutical quality

Principles

Raw materials entering processing and production must meet specified quality requirements.

Source of raw materials

All raw materials must have detailed information about their source, origin, harvesting methods, processing, and storage. These materials must be stored under controlled conditions, monitored, and systematically organized.

Purchasing initial raw materials must be done through contracts with suppliers that include quality and stability guarantees, including reports on changes during harvesting, production, preliminary processing, and raw material processing.

All raw materials before being warehoused must undergo visual and moisture quality checks, along with relevant criteria. There must be tracking records and periodic inspections, recording entries, exits, and inventory levels.

Quality Inspection

All raw materials and initial raw materials used in the production process must meet quality standards.

There must be adequate equipment, trained staff, and approved procedures to perform sampling, testing, and analysis of herbal materials, intermediate products, semi-finished products, and finished products.

Reference samples of herbal materials must be available for use in comparative tests: sensory examination, microscopic examination, and various chemical methods.

Sampling of herbal materials, intermediate products, semi-finished products, and finished products must be carried out using methods and by personnel approved by the quality control department.

Records must be kept to demonstrate that all necessary sampling, testing, and analysis processes have actually been conducted, and any deviations from the process must be fully recorded in the records and investigated.

Test results and analyses of herbal materials, raw materials, intermediate products, semi-finished products, and finished products must be recorded according to established standards.

Sufficient quantities of retained samples of herbal materials, raw materials, semi-finished products, and finished products must be stored to allow for future product testing if necessary.

Storage

Herbal materials must be stored in separate areas. The storage area must be well-ventilated and designed to prevent the entry of insects or other animals, particularly rodents. Measures must be taken to prevent the spread of any animal or microorganism species entering along with the herbal materials and to prevent cross-contamination.

Special attention must be paid to hygiene and maintenance of the storage area, especially when dust is generated.

Herbal materials, extracts, concentrated extracts, or other preparations must be stored under special conditions regarding humidity, temperature, and light; these conditions must be maintained and monitored.

When herbal materials and intermediate products are brought into the warehouse, they must be stored separately in designated areas within the warehouse and labeled accordingly.

A quality control labeling system must be in place: different types of labels must be provided for quarantine, acceptance, and rejection, containing necessary information such as material name, batch number, test number, date of release/disposal, retest date/expiry date. Only designated quality control personnel may apply labels indicating the initial status of the materials.

Rejected herbal materials must be clearly labeled to indicate their status and stored separately and isolated from accepted herbal materials.

2. Personnel, Training

Principles

There must be sufficient qualified personnel to carry out all tasks within the manufacturer's scope of responsibility. Individual responsibilities must be clearly defined, understood by the relevant individuals, and documented in job descriptions.

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There must be sufficient qualified and experienced personnel for each department. There must be a clear separation of personnel in production, testing, and warehousing.

Personnel must be thoroughly trained in herbal processing and manufacturing, holding appropriate qualifications and practical experience in pharmaceutical and herbal drug production.

Heads of production, quality control, and warehousing departments must possess specialized pharmaceutical knowledge, particularly concerning herbal materials.

There must be sufficient key personnel responsible for supervising activities. Supervisors must be trained and hold the necessary qualifications and experience in their assigned fields. Job descriptions and functions of key personnel must be documented.

refers to activities aimed at equipping, updating, and enhancing knowledge of laws, skills, and expertise related to counter-terrorism.

Personnel must undergo training and refresher training. There must be an approved regular annual training program. Personnel must maintain personnel files reflecting their qualifications and training.

3. Factory, Equipment

Principles

The factory must be located, designed, constructed, repaired, and maintained appropriately for the production operations to be performed.

3.1. Storage Area

The storage area must be sufficiently spacious, suitable for the scale of production, with appropriate differentiation and isolation: raw materials and packaged raw materials, intermediate products, semi-finished products, finished products, quarantined products, permitted for export, rejected, returned, or recalled products.

There must be dedicated areas for substances requiring special storage conditions such as solvents, flammable raw materials, toxic substances, psychoactive substances, and similar materials.

Storage areas must be enclosed and locked where necessary.

The storage area must be designed or adjusted to ensure good storage conditions. It must be clean, dry, well-lit, and maintained at acceptable temperatures. Instruments for monitoring humidity and temperature must be available, and records must be kept.

Warehouses must have measures to prevent the entry of insects, rodents, birds, etc.

3.2. Production Area

Special measures must be taken during sampling, weighing, mixing, compounding to facilitate cleaning and prevent cross-contamination when dusty operations occur.

Raw Material Processing/Handling Area

Separate areas must be provided for handling and processing raw herbs such as cleaning, removing impurities, soil, unused parts, washing, cutting, drying, and processing raw herbs (washing area, drying yard or drying room as required). Each processing area must be arranged for easy cleaning and convenient operation. A clean water supply must be available for herb processing to meet hygiene standards.

Herbal Processing Area

It must be separate from other pharmaceutical production areas. Herbal processing areas such as extraction, decoction, stir-frying, separation, etc., must be well-ventilated and ensure the safety and quality of the herbs.

Finished Pharmaceutical Product Manufacturing Area

The factory must be located appropriately, not subject to contamination, designed and constructed to ensure convenient operation, maintenance, and cleaning, and protected from adverse weather effects.

The factory must have defined and appropriately controlled areas for each production process. The factory must be constructed, maintained, and protected against pests such as insects, rodents, birds, and other animals from entering and residing within.

There must be appropriate wastewater systems and waste disposal facilities. There must be potable water and purified water systems to serve production needs.

The design and layout of rooms must ensure unidirectional flow principles for raw materials, personnel, products, and waste to prevent mixing and cross-contamination.

Initial weighing of raw materials must be conducted in a separate weighing area designed for this purpose.

The packaging workshop area must be specially designed and arranged to avoid confusion and cross-contamination.

Lighting systems must be adequately designed and installed to ensure accurate work performance.

The factory must be kept neat, clean, well-maintained, and in good condition.

3.3. Quality Control Area

The testing area must be separated from the production area. Biological and microbiological testing areas must be isolated from each other.

The quality control room must be designed to accommodate the activities to be carried out there, with sufficient space to prevent confusion, cross-contamination, and storage of samples, standards, solvents, reagents, and records.

3.4. Auxiliary Systems

Air Handling System

The factory must have air handling or air conditioning systems separately designed for different areas: production, testing, storage, microbiological testing, and sensitive substance production areas.

Water Treatment System

The factory must have a water treatment system that meets the required standards for drug production and must have a sampling and water quality testing program.

Wastewater Treatment System

The factory must have a wastewater treatment system.

Drainage channels must be large enough, designed, and equipped to prevent backflow. If necessary, open drainage channels should be avoided, but if they are needed, they should be shallow for easy cleaning and disinfection.

Fire Prevention and Firefighting System

A fire prevention and firefighting system must be provided and confirmed to be operational by relevant management authorities.

3.5. Production Equipment

The factory must be equipped with all necessary equipment suitable for producing the required pharmaceutical products.

Equipment must be designed, selected, manufactured, installed, and maintained properly to minimize error risks, allow effective cleaning and maintenance, prevent cross-contamination, dust accumulation, and generally adverse effects on product quality.

Scales and measuring devices must be calibrated according to schedules. Calibration and verification must be fully conducted, and calibration results must be recorded.

Procedures for equipment, tools cleaning and maintenance must be established and strictly followed.

 

3.6. Sanitary Facilities

Sanitary and rest areas must be separated from other areas. Changing rooms, washing facilities must be easily accessible and suitable for the number of users. Toilets must not directly connect to production and storage areas.

4. Sanitation and Hygiene Conditions

Principles

High standards of factory and personal hygiene must be maintained throughout the entire drug production process. The scope of factory and personal hygiene includes employees, factory premises, machinery, equipment, production and packaging materials, cleaning and disinfecting products, and anything that could become a source of contamination.

Sanitation Standards

There must be sanitation inspection standards during production:

- Appropriate cleaning methods must be specified based on the characteristics of the medicinal substances being processed and cleaning materials or equipment.

- Work attire standards.

- Methods for checking employee health conditions.

- Handwashing and sanitizing procedures.

Cleaning Methods

There must be appropriate factory and equipment cleaning procedures. These procedures must be regularly reviewed and approved.

Regular waste disposal measures from production areas must be implemented to maintain cleanliness, waste bins must be clearly marked, emptied, and cleaned at least once daily.

Brushing or compressed air cleaning must be done very carefully, avoiding the use of brushes or compressed air when possible.

Personal Hygiene

Personnel handling medicinal substances must maintain high levels of personal hygiene, receive adequate training on maintaining hygiene conditions. Regulations must prohibit participation in production if suffering from infectious diseases or skin conditions.

Measures must protect personnel from direct contact with harmful substances or allergenic medicinal substances: providing full protective gloves, hats, work clothes, masks, and appropriate footwear during processing.

All personnel must undergo health checks before and during employment. Personnel performing visual inspections must have regular eye examinations.

Personnel must be trained in personal hygiene practices. All personnel involved in production must strictly adhere to high-level personal hygiene regulations. Specifically, personnel must be instructed to wash hands before entering production areas. Signage and rules regarding access control for production, testing, microbiological testing, and warehouse areas must be strictly enforced.

Any individual showing clear signs of illness or open wounds that may adversely affect product quality must not handle initial raw materials, packaging materials, materials during production, or finished products until their health condition is assessed as non-threatening.

All employees must be instructed and encouraged to report to their direct supervisor any condition (relating to the factory, machinery, equipment, or personnel) that they consider may adversely affect the product.

Operating staff must avoid direct hand contact with initial raw materials, directly packaged raw materials, intermediate products, and semi-finished products.

Employees must wear appropriate personal protective clothing.

Smoking, eating, drinking, chewing, and keeping plants, food, drinks, and smoking or medicinal products of individuals are not permitted in production areas, quality control rooms, storage areas, or other areas where such activities could adversely affect product quality.

Personal hygiene procedures, including the use of personal protective clothing, must be applied to all employees entering production areas, whether permanent or temporary staff, or non-staff members such as contractors' employees, visitors, senior management officials, and inspectors.

5. Documentation

Principles

A documentation system must be established to define standards and processes for all raw materials and determine production methods and quality control procedures; to ensure that all employees involved in production understand what needs to be done and when; to ensure that authorized persons have all necessary information when deciding to release a batch of drugs to the market; and to ensure that there are retrievable and available records for inspection purposes. Documentation ensures the availability of data for evaluation, review, and statistical analysis.

5.1. Standards

Initial raw materials, intermediate products, semi-finished products, and finished products must meet full standards and analytical methods. Initial raw materials must comply with the Vietnamese Pharmacopoeia, basic standards, and quality and hygiene regulations of the Ministry of Health.

Standards for initial raw materials and packaging materials

Standards for initial raw materials, primary packaging, and printed packaging, if applicable, should include descriptions of raw materials, including:

- Name (if possible, both the INN name and internal code). For herbal medicines, minimum information such as name and origin (herbal medicine name, scientific name, part used), sensory description must be provided.

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

- Requirements for qualitative and quantitative identification, permissible limits.

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

Packaging materials must meet standards and be compatible with the contents. Raw materials need to be tested for quality standards, defects, and accuracy of identification marks.

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

Standards for intermediate and semi-finished products

Standards must be established 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 should be similar to those for initial raw materials or finished products, as appropriate.

Finished product standards

Finished product standards must include:

- Product name and reference code, if applicable;

- Active ingredient name;

- Formula or formula reference;

- Description of dosage form and packaging details;

- Sampling and testing instructions, or reference to implementation procedures;

- Qualitative and quantitative requirements, with permissible limits;

- Storage conditions and precautions, if applicable;

- Expiration date.

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

Additionally, there must be tests for other relevant criteria 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.

5.2. Production Formulas and Processing Instructions

All products manufactured at the plant must have a detailed original formulation describing the production process. The original formula must be updated and reviewed and accepted by the quality assurance department.

Processing instructions must be established listing different operations performed on raw materials, such as drying, cutting, and grinding, along with the necessary temperature and time for the drying process, and the method used to check particle sizes or sub-particle sizes.

Guidelines for screening or other methods to remove foreign contaminants must be provided. Any process, such as steam sterilization, used to reduce microbial contamination, along with the method to determine the level of this contamination, must be described in detail.

For the production of high-concentration preparations from raw materials, instructions must specify the solvent or medium used, the time and temperature maintained during extraction, and any concentration methods.

Instructions must clearly outline steps in the mixing and adjustment process to achieve the desired active ingredient content and ensure uniformity of the batch after mixing, along with recording parameters during the mixing process.

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

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

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

5.3. Batch Records

There must be a record for each production batch, specifying: Product name, concentration, content; Date of manufacture; Batch number, run number; Full formula of the batch/run; SOPs used and recorded for each process carried out, all major equipment used, all samples, in-process test results, environmental condition test results, equipment pre-use and during-use testing, final packaging label sample retention.

Batch records must conform to the model and fully reflect the original formula.

Batch processing records must be reviewed and appropriately approved.

5.4. Procedures and Record Keeping

Standard operating procedures must guide the cleaning and maintenance of production equipment and tools, specifying: responsibility assignment for cleaning; scheduled cleaning and maintenance of equipment; methods of execution; equipment and raw materials used; instructions for storing cleaned equipment to prevent contamination; monitoring the cleanliness status of equipment before use. These procedures must be strictly followed.

6. Production and In-Process Control

Principles

Manufacturing operations must be conducted according to the registered procedures in the production and circulation permit, with the aim of obtaining products that meet quality requirements.

6.1. Raw Materials

Initial raw material

All initial or crude materials used in the production process must have quality standards and must be tested and found to meet quality requirements.

There must be records of material receipts, dispatches, and inventory levels to allow for verification.

Handling of raw materials and products, such as receiving, storage, sampling, labeling, issuance, processing, packaging, and distribution, must be carried out according to established procedures or written guidelines and documented if necessary.

For animal-derived raw materials, detailed records about the source, origin, and method of production must be kept in the file. These materials need to be stored under controlled conditions and their expiration date or retest date must be clearly indicated.

Raw materials and products that are rejected must be clearly labeled and stored separately in restricted areas. Rejected materials must be safely stored and isolated from accepted materials.

A stock rotation program based on the principle of "first expired, first out" (FEFO) and "first in, first out" (FIFO) must be implemented.

Packaged Materials

The purchase, management, and testing of directly packaged materials and pre-printed packaging must be carried out as for initial materials.

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

Intermediate and Semi-Finished Products

Intermediate and semi-finished products awaiting packaging must be stored separately until quality testing is completed before proceeding to the next stage.

All intermediate and semi-finished product shipments, including additional shipments as required by production, must be accompanied by complete documentation.

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

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

- The correct quantity as per the release order.

- The correct identification of containers.

Sampling

There must be regulations regarding labeling to identify the boxes, packaging of raw materials sampled. Each sample taken must include the following information: sampler's name, quantity of the sample taken, container quantity, sampling date.

Initial raw materials must be stored separately until acceptance and approval for use.

Production Process

Batch Numbering System

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

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

Weighing and Issuing

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

Before weighing and issuing, environmental conditions regarding hygiene, temperature, and humidity must be checked to ensure the weighing and issuing area is clean and the weighing and issuing are accurate. Sterile materials must be weighed and issued in a sterile area. Staff must wear appropriate attire.

Careful measures must be taken to avoid cross-contamination during weighing.

 

There must be a system for managing the issuance of initial raw materials, intermediate products, and semi-finished products.

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

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

There must be a preliminary processing and handling procedure for medicinal materials. When handling medicinal materials, care must be taken to ensure that the handling does not harm the medicinal materials.

Throughout the processing period, all raw materials, packaging containers for semi-finished products, precision machinery and equipment, and if applicable, rooms and packaging lines in use must be labeled or marked with product or raw material names being processed, concentration (if applicable), and batch numbers. All inappropriate labels and signs present prior to processing must be completely removed.

Tablet presses without their own enclosed environments must be placed in separate areas. Weight and hardness tests of tablets must be conducted during tablet pressing.

For capsule production, weighing of capsules must be carried out throughout the encapsulation process.

Tablets or capsules taken from a press station 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 exposure.

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

Liquids, creams, and topical medications must be produced using methods and conditions that avoid bacterial and other contaminations.

The production and transportation of liquids, creams, and powders must be carried out in a closed system.

Water used in the production of finished herbal medicine products must meet at least purified water standards.

Intermediate and finished products

A storage and release system for semi-finished and finished products, including clearly identifying the status of the product (storage, release, rejection), must be established. Procedures for handling non-conforming products and returned products must be developed.

Production process control

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

6.3. Labeling, Packaging, and Distribution

Packaging

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

 

Labeling and Packaging Activities

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

Storage and Distribution

SOPs for storing finished products in shipping areas must be established. Records must be maintained to quickly identify all customers who purchased a specific batch of finished products, specifying the shipment date, quantity, packaging specifications, and delivery details for each batch to customers. Documentation regarding storage time, temperature, and other storage conditions prior to distribution must be retained.

6.4. Sanitation in Production

Measures must be implemented to control the use of insecticides to prevent product contamination.

Wastewater, waste, rejected raw materials, and unacceptable materials must be controlled and/or treated safely and hygienically. Employee movement in restricted access areas must be regulated.

7. Quality Control Testing

Principles

The quality control department must be independent and managed by a person with appropriate qualifications and experience, capable of overseeing one or more laboratories. Adequate resources must be available to ensure that all quality control measures are effectively and reliably implemented.

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Quality control personnel must have specialized knowledge about herbal medicine products to conduct qualitative tests, detect counterfeits, check for mold or insects, and assess batch uniformity of herbal medicines.

The quality control laboratory must have adequately trained and experienced staff to complete assigned tasks.

Equipment

The quality control laboratory must be designed to accommodate specialized equipment, documentation, and workspace for personnel.

The quality control laboratory must be equipped with suitable machines and tools for sampling, analysis, calibration, and data processing. Analytical equipment must be compatible with testing methods and meet the unit's quality control requirements. The physical testing laboratory is equipped with instruments to test physical parameters (drying ovens, furnaces, disintegration testers, thin-layer chromatography, incubators) and production process monitoring equipment. For expensive equipment such as gas chromatography or difficult tests like base sterility, external service units can be utilized for testing. Test results must be systematically recorded for long-term tracking.

Records and Documentation

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

Analyst notebooks record results, calculations, data, and relevant observations for sample analysis. Notebooks must be numbered and not written in pencil, erased, or overwritten.

The analysis dossier must contain all information about the sample, testing method, analytical results, and must be pre-printed with the minimum information as follows:

- Sample name, origin/place of production, reference code if available.

- Batch number, expiration date, analytical requirements (number, date, and content).

- Date of receipt, person who received the sample.

- Standards and testing methods.

- Condition of the sample upon receipt and before analysis.

- Analytical results (including calculations).

The analysis dossier must be stored in the testing file along with the analytical results. The analysis report must have the signature of the tester and the supervisor's name.

All necessary quality standards for testing work must be updated and retained, including:

- The 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.

Stability monitoring

There must be a program and dossier for monitoring drug stability. Drug stability monitoring dossiers must be retained.

8. Complaints and product recalls

Product complaints

Written procedures must be established to handle all complaints and designate responsible persons for forwarding, reviewing, and evaluating product complaints. Handling of product complaints must be documented in writing and retained for a certain period.

Returned products

Written procedures must be established to accept and examine returned pharmaceuticals and establish a tracking dossier for returned products. The dossier for returned products includes the following contents: product name and dosage, formulation type, batch number, return reason, quality of returned product, return date, final decision and date.

Returned products must be clearly identified and stored in a segregated area.

Product recall

Written procedures must be established to handle product recalls and specify the authority to decide on recalling a product. A dossier and report on product recall must be established and retained, including the results of the recall and containment actions. Recalled products must be stored in a secure location to prevent their reintroduction into circulation and use without investigation and evaluation.

9. Inspection and self-inspection

An internal inspection program must be established and appropriate inspection team members determined. Internal inspections must be recorded and an internal inspection report prepared to take appropriate corrective actions.