Part 2 Good Manufacturing Practices for Pharmaceuticals
Chapter 2 Good Manufacturing Practices for Chinese Herbal Medicines
Section 1 General Provisions
Terms used in Chapter 2 are defined as follows:
(1) Raw materials: any materials used in the manufacture of pharmaceuticals, including those that do not remain in the end product.
(2) Semi-finished or intermediate products: any products that are obtained during the manufacturing process, and that, with further processing, can become finished products.
(3) Products: active pharmaceutical ingredients, or preparations that contain active pharmaceutical ingredients and may contain other non-active ingredients, for which all manufacturing processes have been completed.
(4) Labeling: refers to all text and graphics that appear on labels, instruction sheets or packages, or that come with products.
(5) Packaging materials: include product containers, caps, and any materials used in the outer packages of products.
(6) End products: refer to pharmaceutical products that have been packaged, and whose outer packaging clearly indicates the contents therein.
(7) Batch: refers to a specific amount of pharmaceutical or other substance produced under a single set of manufacturing instructions, and that is consistent in character and quality. However, under conditions of continuous production, a batch refers to a specific amount of pharmaceutical or other substance produced within a specific time period, or that, within specific parameters, is consistent in character and quality.
(8) Batch number: refers to any definite combination of letters, numbers or other symbols that can be used to look up comprehensive information on a batch of products or other substances.
(9) Content: the unit quantity of the components of a pharmaceutical.
(10) Validation: written documentation attesting that any procedure, manufacturing process, mechanical device, raw material, action or system is capable of achieving its anticipated effect.
(11) Active pharmaceutical ingredient: an active substance or ingredient that is produced through physical, chemical processes for use in the manufacture of a pharmaceutical product.
(12) Tamper-proof packaging: packaging with an identifying mark or barrier that enables consumers to clearly identify the contained product.
(13) Clinical trial drug: a pharmaceutical or placebo that is undergoing clinical trials, and has not yet obtained approval.
Chinese herbal medicine manufacturers shall implement validation procedures; the categories to be implemented, as well as the implementation methods and schedule, shall be announced by the central competent health authority.
The manufacturing, processing, re-packaging and packaging of raw materials of Chinese herbal medicine shall be governed by the provisions of Chapter 2; the categories to be implemented, as well as the implementation methods and schedule, shall be announced by the central competent health authority.
Section 2 Environmental Sanitation
In treating hazardous waste materials, toxic containers, hazardous gases, dust, wastewater, biological components and other hazardous components or materials, Chinese herbal medicine factories shall act not only in accordance with relevant laws, but also with the following principles:
(1) For hazardous waste materials and toxic containers, storage facilities shall be established, and these materials and containers shall be decomposed in accordance with their properties, and then appropriately incinerated or buried. If toxic containers are to be reused, they shall be washed and rigorously controlled, and may not be used to hold food products.
(2) For hazardous gases and dust, airtight facilities, local exhaust ventilation systems and negative pressure procedures shall be established; these substances shall, in accordance with their properties, be scrubbed, collected, oxidized, reduced, combusted, or otherwise appropriately treated. If exhaust gas contains dust, it shall first be subjected to centrifuging, filtering, scrubbing, or some other form of dust-removal processing; the emission of such gases must comply with air pollutant emission standards.
(3) For the processing of wastewater, impermeable storage pools shall be established, and acidification, alkalization, neutralization, active carbon adsorption, or other effective methods shall be used to break down or remove wastewater toxins; the release of wastewater must comply with water release standards.
Section 3 FactoryBuildings and Facilities
Chinese herbal medicine factory buildings shall be well constructed and safe; manufacturing, processing and packaging areas shall be completely separated from offices, reception rooms, laboratories, restaurants and their associated lavatories; the use of asbestos shall be avoided.
The buildings described in the preceding Paragraph shall be designed to prevent the entry of rodents, insects and dust; interior ceilings, walls and floors shall be smooth and free of cracks and crevices, easy to clean, and non-conducive to the collection of dust; where necessary, materials that are easily cleaned and disinfected, such as epoxy resins shall be used. Interior ducts shall be constructed of materials that do not easily collect dust, and shall be hidden where possible; drainage facilities and drainage exits shall be equipped to prevent wastewater backflow.
Areas at Chinese herbal medicine factories used for the storage of raw materials, product containers, caps, and labeling and packaging materials, and for the manufacture, processing, re-packaging, packaging and storage of products, shall be appropriately sized and located. These areas shall be suitably arranged, with operation areas clearly delineated by production type. Moreover, appropriate work space and levels of insulation and cleanliness shall be established as needed.
Levels of cleanliness, as mentioned in the preceding Paragraph, shall be established in accordance with the type of product being manufactured. Operation areas requiring the same level of cleanliness shall be grouped together; buffer zones or entry rooms shall be established between areas with different levels of cleanliness, and different colors or types of work clothes may be used to indicate the cleanliness levels of the various operation areas.
No operation area may be used as a passageway by personnel from other operation areas; passageways for people and for the transport of goods shall be separate, and shall not cross.
Facilities for the storage of raw materials, product containers, caps, labeling and packaging materials, semi-finished or intermediate products, and products shall be given “pre-inspection,” “approved for use” and “not approved for use” designations; if items are present that need to be kept frozen or toxic, appropriate storage facilities shall be established.
Semi-finished or intermediate products shall be stored separately; if they are not stored separately, special care shall be taken to prevent contamination and degradation of quality.
Where Chinese herbal medicine factories manufacture environmental sanitation agents, environmental sanitation agent manufacturing, processing and re-packaging areas, as well as raw material storage facilities, shall be separated from pharmaceutical manufacturing, processing and re-packaging areas by a distance of no less than eight meters.
Where Chinese herbal medicine factories manufacture pharmaceutical feed additives, the pharmaceutical feed additive operation area shall be independent from other operation areas.
Where Chinese herbal medicine factories use their pharmaceutical production facilities to manufacture food products, cosmetics or general goods, care shall be taken to prevent cross-contamination, and validation procedures shall be carried out.
All operation areas in Chinese herbal medicine factories shall be equipped with appropriate illumination and ventilation facilities; where necessary, aforesaid areas shall also be equipped with appropriate facilities for the regulation of temperature and humidity.
Each production and processing area shall, in accordance with its air purity requirements, be equipped with appropriate air filtration systems, including pre-filters and particulate filters.
In areas for the storage of raw materials, products, semi-finished or intermediate products, and areas where products are manufactured, processed, re-packaged or packaged, conditions conducive to the prevention of quality degradation shall be maintained.
For Chinese herbal medicine factory production areas involving hazardous or flammable raw materials, solvents, semi-finished or intermediate products, or products, appropriate protective, first-aid and segregation facilities shall be established.
Facilities used in the manufacturing, processing and re-packaging process shall be airtight from start to finish; where facilities are not airtight and dust or hazardous gases are produced, local exhaust ventilation systems and negative pressure procedures shall be established.
Lighting, switches, sockets, motors and other electric devices for operation areas that produce dust, where organic solvents are used, or where hazardous substances are present, shall, as needed, be explosion-proof, airtight, or isolated from operation area.
Boilers, pressure vessels, cranes and other types of dangerous equipments and facilities shall be inspected and approved in accordance with relevant regulations before use.
Chinese herbal medicine factories shall, as needed, establish employee lounges and shower rooms outside of work areas.
Manufacturing and processing areas shall be installed with appropriate lavatory facilities, and wastewater, garbage and other waste materials produced in aforesaid areas shall be treated in a safe and sanitary manner. Lavatory facilities shall be separated from work areas.
Chinese herbal medicine factories shall, as needed, install facilities for the processing of general use and wastewater, and facilities for the production of boiler water or distilled water. Water supply facilities shall be kept from contaminating products.
Container washing facilities shall be installed in Chinese herbal medicine factories.
Section 4 Facilities
Facilities at Chinese herbal medicine factories used for the manufacture, processing, re-packaging, packaging and storage of products shall be appropriately designed, sized and located for ease of usage, cleaning and maintenance.
Facilities needed for the production of different dosage forms shall be positioned according to manufacturing process sequence.
The surfaces of facilities at Chinese herbal medicine factories that come into direct contact with raw materials, semi-finished products, intermediate products or products shall be made of non-reactive, non-releasing and non-adsorptive materials; where any process requires the use of lubricants, coolants or other similar substance, aforesaid substances may not come into contact with raw materials, product containers, caps, semi-finished products, intermediate products or products.
Facilities and appliances at Chinese herbal medicine factories used for the manufacturing, processing, re-packaging, packaging, and storage of the products shall be cleaned and maintained regularly, and written operation procedures shall be established.
The production capacities of mechanical facilities used at Chinese herbal medicine factories to produce a single product shall be carefully coordinated to ensure consistency of product quality.
Automated machinery and electronic facilities used in the manufacturing process, as well as software and equipment related to computers or to the manufacture, processing, re-packaging, packaging or storage of pharmaceuticals, shall be regularly recalibrated, inspected, examined and maintained.
Computer systems used to control production and production management records shall be properly maintained, and alterations may not be made to aforesaid systems without permission from the personnel in charge; all data that is input or printed shall be checked for accuracy, and its period of validity shall be determined based on the complexity and reliability of the computer system.
Air used by drying facilities during the manufacturing process shall first be treated with a purification filter.
Facilities used to manufacture pharmaceuticals for internal and external use shall be kept strictly separate, and may not be used interchangeably.
Pharmaceutical factories shall install weighing facilities that comply with regulations, and shall recalibrate aforesaidfacilities regularly.
Chinese herbal medicine factories shall keep facilities and equipment for the production of pharmaceuticals for human and animal use separate, and these two types of production may not be carried out in the same structure unless the two areas are completely separated. However, pharmaceuticals for animal use that comply with the standards governing drugs for human use are not subject to this restriction.
Chinese herbal medicine factories shall, in accordance with the requirements of the products being manufactured, install necessary manufacturing, processing, re-packaging and packaging facilities.
Chinese herbal medicine factories shall, in accordance with their specification testing requirements for raw materials, semi-finished products, intermediate products and products, establish testing departments and appropriate testing facilities. However, if tests are conducted on a contract basis by an organization approved by the competent authority, in accordance with the Contract Drug Manufacturing and Testing Operating Principles, and clear documentation is provided, establishment of aforesaid facilities may be waived.
Testing departments shall include testing and instrument laboratories. Instrument laboratories shall be separate from testing laboratories, and shall be kept at an appropriate temperature and level of humidity and air purity; testing laboratories shall be installed with sufficient and easy to use test benches, test stands, drug cabinets, fume hoods, water supply and washing facilities, as well as electric heating, thermostatic and drying facilities, and shall also be stocked with utensils and containers, chemical reagents and solutions, standard solutions and other necessary items.
Areas, facilities and equipment necessary for total viable count and other microorganism tests shall be installed as needed; microorganism strains, culture mediums, and animals necessary for conducting bioassays shall be adequately stocked and maintained.
For pyrogen testing, priority shall be given to replacing testing on live animals with alternative techniques.
Section 5 Organization and Personnel
Quality control departments and manufacturing departments at Chinese herbal medicine factories shall be established separately.
A person shall be placed in charge of each Chinese herbal medicine factory department, and sufficient personnel shall be assigned to carry out and supervise the manufacture, processing, re-packaging, packaging or storage of each product.
The person in charge, supervisors and employees of each Chinese herbal medicine factory department shall all possess suitable educational backgrounds, and shall all undergo practical training in implementing the rules prescribed in Part 3 of this set of Standards; Microbiological testing personnel shall receive specialized trainings.
Chinese herbal medicine factories shall establish in writing sanitary standards for employees; the standards shall include the following items:
(1) Regular health examinations in accordance with the nature of the employee’s job;
(2) Measures to prevent employees with illnesses or open wounds from having a negative impact on pharmaceutical safety or quality;
(3) Rules requiring employees to wash or disinfect their hands when entering work areas, refrain from wearing jewelry, eating, drinking, smoking, or engaging in any other behavior that may impact sanitation in manufacturing areas;
(4) Standards for the types of work clothes, hoods, face masks, gloves, arm covers, and shoe covers for each job.
Section 6 Management of Raw Materials and Product Containers and Caps
Chinese herbal medicine factories shall establish detailed quality specifications for raw materials and product containers and caps, as well as operational procedures for the acceptance, labeling, storage, handling, sampling, testing and inspection of these items.
Containers that hold raw materials, product containers or caps shall be clearly labeled with batch numbers and status, pending-inspection, approved for use, not approved for use, or to be isolated; this information shall be entered into the disposition record of each batch.
Container caps shall, as needed, be fitted with children safety devices to prevent accidental consumption.
When Chinese herbal medicine factories receive shipments of raw materials, product containers or caps, they shall collect representative samples from each batch for testing; a note of this action shall be made on the original container.
Containers holding the samples described in the preceding Paragraph shall be appropriately labeled to facilitate tracking of sample names, batch numbers, sampling basis, original container and name of sampler.
The samples referred to in the preceding Article shall be tested in accordance with the following principles:
(1) Every raw material shall be tested to determine whether it is in compliance with documented specifications. However, aside from identification tests, other tests may be waived if the test reports provided by the supplier are evaluated and found to be reliable.
(2) Products containers and caps shall be tested to determine whether they are in compliance with established specifications.
(3) Where raw materials, product containers or caps are susceptible to contamination by filth, insects, foreign objects or microorganisms, thus affecting their intended uses, relevant test items and methods shall be included in the quality specifications for aforesaid items, and each batch shall be inspected for contamination.
Where raw materials, product containers or caps are tested and found to be in compliance with documented specifications, Chinese herbal medicine factories may approve them for use; where aforesaid items are not in compliance, they shall not be approved for use.
Raw materials, product containers or caps that are approved for use shall be used in the order of approval. However, where aforesaid items have been stored for long periods, exposed to the air or high temperatures, or subjected to other detrimental conditions, retesting shall be carried out.
Raw materials, product containers or caps that are not approved for use shall be labeled to this effect, and kept isolated prior to their proper disposal.
Section 7 Manufacturing Process Control
To insure that each product batch is of consistent quality, Chinese herbal medicine factories shall have designated personnel establish process control standards for every product, and have announced the standards independently reviewed by other personnel.
The process control standards mentioned in the preceding Paragraph shall include the following items:
(1) Product name, content and dosage form;
(2) Name and weight or volume of each active ingredient per product by unit weight, volume or dosage form, and total weight or volume of unit dosage form;
(3) Names and specifications of all raw materials; if a code name or number is used to represent a raw material, aforesaid code shall be sufficient to determine the nature of the material;
(4) Quantity of each product batch;
(5) Weight or volume required by each raw material for each product batch. However, the quantities of raw materials used to produce a given dosage form may be increased or varied within a reasonable range; aforesaid range shall be explained in the manufacturing process control standards;
(6) Appropriate theoretical weights or volumes for each stage of the manufacturing process;
(7) Theoretical production quantity, including upper and lower production quantity limits expressed as percentage;
(8) Product container, cap and packaging material specifications (along with label signed and dated by inspector and samples or copies of all other labeling);
(9) Complete manufacturing and control manuals, sampling and test procedures, specifications and guidelines.
Chinese herbal medicine factories shall establish in writing process control procedures; aforesaid procedures shall be approved by the quality control department. Where actual operations deviate from documented procedures, aforesaid deviation shall be recorded, a determination of how to handle the deviation shall be made, and an explanation shall be given.
To insure the each product batch is of consistent quality and integrity, Chinese herbal medicine factories shall take steps to evaluate and validate the consistency of process control operations, including related equipment and facilities, for each product; documented procedures for the validation of each manufacturing process shall also be established, and shall be complied with and validated on a regular basis.
All original verification records and statistical analysis data related to evaluation and validation procedures shall be compiled and filed for future reference.
Chinese herbal medicine factories shall clearly mark the contents and product batch manufacturing stage dates and times of mixing and storage containers, production lines and main manufacturing facilities used in the production and manufacture of each product batch, and enter the information into the batch manufacturing records.
In regard to the quantities of raw materials used by Chinese herbal medicine factories in the manufacture of products, the amounts of active ingredients in each product batch may not fall below the nominal quantity.
Weighing, dividing and other procedures carried out on raw materials shall be performed in designated segregation areas, and shall be appropriately supervised and controlled.
Documented operational procedures shall include detailed test and control procedures for representative samples from each batch of semi-finished or intermediate products.
During the manufacturing and production process, the quality control departments of pharmaceutical factories shall carry out tests on semi-finished or intermediate products in accordance with established test procedures, thereby determining whether to approve aforesaid products for use; semi-finished or intermediate products that are not approved for use shall be labeled to this effect and kept isolated.
Chinese herbal medicine factories shall include appropriate measures to prevent contamination by harmful microorganisms in written operation procedures.
Section 8 Management of Packaging and Labeling
Chinese herbal medicine factories shall establish in writing management procedures for the acceptance, labeling, storage, handling, sampling and testing of packaging and labeling materials.
Where over-the-counter drug products for human use are produced, packaging for aforesaid products shall be tamper-proof, and shall be kept intact during the manufacturing, shipping and retail display process; moreover, aforesaid packaging shall be designed in such a manner that tampering is easily detectable by consumers.
Prior to the acceptance or use of labeling and packaging materials, representative samples shall be taken from each batch for testing; testing results shall be recorded and samples preserved. Where test results comply with established specifications, aforesaid materials may be approved for use; where aforesaid materials are not in compliance, they shall not be approved for use.
Chinese herbal medicine factories shall, in accordance with product type, content and dosage form, separately store and appropriately mark labels and other labeling materials; storage areas for aforesaid materials may not be entered without the consent of the personnel in charge.
Packaging or labeling materials that have expired or are not approved for use shall be returned or destroyed. The amounts of labeling materials received, used and returned shall be kept track of, and no discrepancies shall be allowed.
Unused portions of labeling materials printed with batch numbers shall be destroyed; unused labeling materials that are not printed with batch numbers shall be appropriately identified and stored.
Prior to packaging and labeling products, Chinese herbal medicine factories shall first inspect packaging and labeling materials to ensure that they are correct and suitable for use; aforesaid inspection results shall be entered into the batch manufacturing record.
Packaging and labeling facilities shall be inspected prior to use to ensure that all pharmaceuticals from the previous run and packaging and labeling materials not suited to the present run have been completely removed; aforesaid inspection results shall be entered into the batch manufacturing record.
During the final stage of production, products that have already been packaged and labeled shall be inspected to ensure that every container or package is correctly labeled.
To ensure that the ingredients, contents, quality and purity of products ready for use are in compliance with established specifications, Chinese herbal medicine factories shall, unless other regulations apply, label aforesaid products with a usage period or expiration date as determined through stability testing; products that must be prepared before use shall be clearly labeled with the method of preparation and usage period following preparation.
Section 9 Storage, Shipping and Sales
Chinese herbal medicine factories shall establish in writing product storage procedures; aforesaid procedures shall include the following items:
(1) Segregation measures for products awaiting approval for use;
(2) Appropriate temperature, humidity and light exposure standards to ensure that product ingredients, contents, quality and purity are not adversely affected by storage.
Chinese herbal medicine factories shall establish in writing shipping and sales procedures; aforesaid procedures shall include the following items:
(1) Measures to ensure that products are sold in the order of manufacture;
(2) Shipping and sales methods that ensure product ingredients, contents, quality and purity are not adversely affected by environmental factors;
(3) Systems to ensure prompt recycling.
Section 10 Quality Control
Chinese herbal medicine factories shall establish in writing quality department duties and operational procedures; aforesaid duties and procedures shall include the following items:
(1) Examination of approval, non-approval and manufacturing records for all raw materials, product containers, caps, semi-finished or intermediate products, packaging materials, labeling materials and products;
(2) Examination of operational procedures specifications that affect product ingredients, contents, quality and purity;
(3) Inspection of facilities used in the testing of raw materials, product containers, caps, semi-finished or intermediate products, packaging materials, labeling materials and products;
(4) Establishment in writing of operational procedures governing the calibration of instruments, devices, meters and recording apparatuses; aforesaid procedures shall clearly prescribe calibration methods, schedules, accuracy limits, as well as usage restrictions and remedial measures for items that do not comply with accuracy limits;
(5) Establishment in writing of operational procedures governing sample quantities, test intervals and test methods for product stability testing.
Specifications, standards, sampling plans, test procedures, and test control measures established for the various departments of a Chinese herbal medicine factory, and any alterations related to aforesaid items, shall be examined and approved by the quality control department of aforesaid factory prior to implementation.
Chinese herbal medicine factories shall faithfully follow the operational guidelines that they have established and keep records of the implementation process; where a deviation from aforesaid guidelines occurs, aforesaid deviation shall be recorded, a determination of how best to handle the deviation shall be made, and an explanation shall be given.
Chinese herbal medicine factories shall select senior specialist personnel from each department to establish a quality assurance team or committee to advice, review and supervise activities related to quality system.
Chinese herbal medicine factories shall test every batch of products to ensure that they are in compliance with established specifications; each batch of products that must not contain harmful microorganisms shall, where necessary, be subjected to appropriate tests.
Representative samples shall be removed from each batch of products or end products, and taken from the raw materials containing active ingredients used in making aforesaid products, and placed in reserve; aforesaid reserve samples shall be stored under indicated conditions, and shall be of at least twice the quantity needed for all required tests.
Reserve samples shall be retained until one year after the expiration date of the product from which it was taken; reserve samples of products that do not require expiration dates shall be kept for at least three years after the date of dispatch of the last batch of aforesaid product.
Section 11 Records and Reports
The manufacturing, control, shipping and sales records prescribed in Chapter 2 shall all be stored in suitable locations, made available for inspection, and used at least once a year in the assessment of product quality standards; aforesaid records shall be kept until one year after the expiration date of the batch of products or end products in question. However, records for products that do not require expiration dates shall be kept for three years after the date of dispatch of the batch of products or end products in question.
When relevant competent authorities make inspections, they may photocopy, or copy by other means, the records described in Paragraph 1 or copies of aforesaid records.
Chinese herbal medicine factories shall keep batch manufacturing records for each batch of products produced; aforesaid records shall contain comprehensive manufacturing and quality control information on the product batch in question.
Chinese herbal medicine factories shall produce accurate copies of manufacturing management standards, verify the accuracy of aforesaid copies, and sign and date them.
Chinese herbal medicine factories shall make detailed records of the important steps in the manufacture, processing, re-packaging, packaging and storage of each batch of products; aforesaid records shall include the following items:
(1) Date and product batch number;
(2) Identification marks for each batch of raw materials and semi-finished or intermediate products;
(3) Identity of major facilities and production lines;
(4) Quantity and volume of raw materials used in product processing;
(5) Manufacturing process, testing and control results;
(6) Pre- and post-use inspection of labeling and packaging areas;
(7) Ratio of actual production output to theoretical output at appropriate stages of manufacturing process;
(8) Comprehensive labeling control records, including samples or copies of all labeling;
(9) Product container and cap identification marks and usage quantity;
(10) Sampling record;
(11) Dates and times of each major step in the production process, as well as signatures and dates for operation personnel, direct supervisors or inspectors involved in each step.
The test records produced by Chinese herbal medicine factories shall include all test data used in determining compliance with established specifications and standards; aforesaid data shall include the following items:
(1) Sampling location, quantity, batch number or other clear identifying code, sampling date, and date of test completion;
(2) Basis of all test methods;
(3) Weight or volume of all samples tested;
(4) Comprehensive records of all data generated during testing process, including charts, graphs and spectra produced by test instruments, and clearly listing all the raw materials, product containers, caps, semi-finished products, intermediate products or products tested, along with the batch numbers of aforesaid items;
(5) Record of all test-related calculations;
(6) Records of test results and comparison of aforesaid results with established specifications;
(7) Names and dates for all personnel involved in conducting tests;
(8) Signatures of inspectors testifying that the original records inspected are accurate, truthful and in compliance with established specifications.
The manufacturing and quality control records (including packaging and labeling control records) for all products manufactured by Chinese herbal medicine factories shall be examined by the quality control departments of aforesaid factories to ensure that all products are in compliance with all established documented operational procedures prior to release, shipment or sale.
Where the theoretical production quantity exceeds the upper or lower production quantity limits prescribed by manufacturing control standards, or if any other similar discrepancy occurs, or if any batch or raw material does not conform to specifications, a thorough investigation shall be conducted even if aforesaid batch of products has already been shipped or sold; such investigations shall be extended to other batches of the product in which aforesaid discrepancy occurred, and to any other products that may be affected by aforesaid discrepancy.
Written records shall be kept of the investigations described in the preceding Paragraph; aforesaid records shall include investigation conclusions and methods.
Chinese herbal medicine factory’s shipping and sales records shall include products names, contents, dosage forms, recipient names and addresses, and shipping dates and quantities.
Chinese herbal medicine factories shall make written records of product complaints, and keep aforesaid records in product complaint files; aforesaid files shall be stored in a suitable location, or in a facility where they can be easily accessed for inspection.
The written records referred to in the preceding Paragraph shall be kept until the expiration date of the product in question, or for one year after the complaint was received, whichever period is longer. However, for products that do not require expiration dates, aforesaid records shall be kept for at least three years after the date of dispatch of the product in question.
Records of returned products kept by Chinese herbal medicine factories shall include product names, contents, batch numbers, reasons for return, quantities, disposition dates, final disposition methods; aforesaid records shall be kept in accordance with the regulations prescribed in Article 81.
Section 12 Handling of Complaints and Returned Products
Chinese herbal medicine factories shall establish in writing procedures for the handling of oral and written complaints from consumers; all oral and written complaints shall be investigated and assessed by the quality control departments of aforesaid factories.
Where Chinese herbal medicine factories discover serious and unanticipated product defects, they shall report aforesaid defects to the relevant competent authorities, and handle aforesaid defects in accordance with the stipulations of the Act.
Written records shall be kept of the handling of all complaints; aforesaid records shall be properly collated and filed.
Chinese herbal medicine factories shall properly identify and separately store returned products. If there are any doubts regarding a product’s safety, ingredients, contents, quality or purity due to storage or shipping conditions, the condition of the product, container, packaging or labeling, or any other relevant circumstances either before or after the product is returned, unless the product’s safety, ingredients, contents, quality and purity are confirmed to be in compliance with established specifications through testing or investigation, aforesaid product shall be destroyed. However, where aforesaid product can be brought into compliance with established specifications through remanufacturing, remanufacturing may be carried out.
Section 13 Pharmaceuticals for Use in Clinical Trials
The production and manufacturing of Chinese herbal medicine for use in clinical trials by Chinese herbal medicine factories shall, unless otherwise regulated by regulations of this Chapter, be governed by other relevant regulations prescribed in this Part.
Where Chinese herbal medicine factories have not yet established validated manufacturing processes for Chinese herbal medicine for use in clinical trials, or have not yet established comprehensive manufacturing control standards, aforesaid factories shall establish in writing operational procedures and keep detailed and accurate records for each batch of products manufactured and each batch of raw material used. Batch manufacturing records shall be kept until clinical trials are completed, or until at least two years after the product is completed, whichever period is longer.
Where Chinese herbal medicine factories produce Chinese herbal medicine for use in clinical trials, aforesaid Chinese herbal medicine, in addition to complying with regulations governing labeling in the Act, must also be labeled “for use in clinical trials only,” and marked with the name of the party that commissioned the clinical trial and a trial code sufficient to identify the trial location and research personnel involved. However, where pharmaceuticals for use in clinical trials are tested in closed trials (double-blind trials), drug name, potency and efficacy may be replaced by product codes, serial numbers and packaging batch numbers.
Chinese herbal medicine factories shall determine suitable expiration dates for Chinese herbal medicine for use in clinical trials based on the product properties, container characteristics and storage conditions; the expiration dates marked on aforesaid Chinese herbal medicine may not exceed the expiration dates marked on the original product packaging.
Where clinical trials do not provide stability testing information, the usage period of a repackaged product may not exceed 25% of the remaining portion of the usage period of the original bulk product, or the six-month period following repackaging, whichever period is shorter.
Where a Chinese herbal medicine factory has a Chinese herbal medicine for use in clinical trials manufactured or tested on a contract basis, aforesaid contract shall clearly state that the product in question is for use in clinical trials only.
Where Chinese herbal medicine factories destroy Chinese herbal medicine for use in clinical trials, destruction of aforesaid Chinese herbal medicine may not take place until all clinical trials and the final report are completed; detailed records shall be kept of the destruction process, and aforesaid records shall be preserved by the manufacturer.