GOOD MANUFACTURING PRACTICE FOR PHARMACEUTICAL
PRODUCTS (Revised in 1998)
Annex
Chapter I-General Provisions
1. This annex stipulates the supplemental requirements to Good Manufacturing Practice for
Pharmaceutical Products (revised in 1998) issued by the State Drug Administration, specified for
manufacture and quality management of sterile pharmaceutical products, non-sterile
pharmaceutical products, active pharmaceutical ingredients, biological products, radioactive
pharmaceuticals and traditional Chinese medicine preparations.
2. Air cleanliness of a clean room (area) for pharmaceutical production is classified into four
grades:
An Air Classification System for Clean Rooms (Areas)
Class
Max. Number of particles
permitted per m3
Max. Number of viable
microorganisms permitted
≥0.5μm
≥5μm
Air sample
CFU/m3
Settle plates
CFU/plate
100
3,500
0
5
1
10,000
350,000
2,000
100
3
100,000
3,500,000
20,000
500
10
300,000
10,500,000
60,000
-
15
3. Control of clean rooms (areas) shall meet the following requirements:
(1) The number of personnel in clean areas shall be strictly controlled and minimized. All persons
employed in such areas (including those concerned with maintenance and others) shall be trained
and checked periodically in aspects of basic knowledge of sanitation and microbiology as well as
operation, etc. When temporary staff or outsider need to be brought in, a particular care shall be
taken over their supervision.
(2) Airlocks shall be set between clean and non-clean rooms (areas), and the flows of personnel
and materials shall be arranged properly.
(3) Floor drains shall be excluded from a class 100 room (area). Operators shall not work with
bare hands, and hands shall be disinfected from time to time if inevitable.
(4) A conveyor belt shall not pass through a partition between Class 10,000 and lower air
cleanliness.
(5) Working clothes used in Class 100,000 or higher class shall be laundered/ cleaned in
corresponding areas, and sterilized if necessary.
(6) Surfaces of insulation of equipment in a clean room (area) shall be smooth so as to minimize
the shedding of particles.
(7) Cleaning tools used in a clean room (area) shall be made of such materials as to minimize the
shedding of particles and permit the effective cleaning and sanitation. They shall be used in
defined areas and kept in dedicated places to prevent contamination.
(8) Particles and viable microorganisms from air samples and settle plates in a clean room (area)
under the static condition shall comply with the specified requirements, and be monitored
regularly under dynamic condition.
(9) If clean air is recycled, effective measures shall be taken to avoid contamination and
cross-contamination.
(10) Air handling system shall be cleaned, maintained, and documented according to written
procedures.
4. Validation of pharmaceutical manufacturing processes shall include:
(1) Air handling system
(2) System of process water
(3) Production process and its change
(4) Cleaning procedures for equipment
(5) The changes of active pharmaceutical ingredients and excipients.
In addition, the following items shall be validated for sterile pharmaceutical products.
(1) Equipment for sterilization
(2) Filtration and filling/sealing systems including aseptic filling of powder
5. The water system shall be designed, installed, and maintained in such a way to comply with the
specified quality standards.
6. Packaging materials printed with the same content as those of labels shall be controlled as
labels.
7. Only remnant products of two batches are allowed to be packed in one carton/box. The two
batch numbers shall be indicated on the package, and records shall be made.
8. Batch review shall be performed by quality management department, including the records of
dispensing, line clearance, in-process control handling of deviation, and testing results of products.
No hatch of products shall be released prior to certification by quality management department ~n
accordance with all the specified requirements.
Chapter Ⅱ-Sterile Pharmaceutical Products
Sterile pharmaceutical products refer to those for which sterility test is included in official
specifications
1. The air cleanliness of production environment for sterile products is required as follows:
(1) Terminally sterilized products.
Class 100 or class 100 with class l0,000 background: Filling of large volume parenteral (LVP)(≥
50ml).
Class 10,000: Preparation and filtration of dilute solution; Filling of small volume parenteral
(SVP);
Final handling of packaging materials that come into direct contact that solution.
Class 100,000: Preparation of primary concentrate solution, or dilute solution in a closed system
(2) Aseptically prepared products.
Class 100 or class 100 with class 10,000 background: Preparation of solution without aseptic
filtration before filling; Filling of solutions or powders and stoppering; Exposing environment for
the final handled packaging material that come into direct contact with products.
Class 10,000: The preparation of solutions with aseptic filtration before filling.
Class 100,000: Capping and final washing of packaging materials that come into direct contact
with products.
(3) Other sterile products.
Class 10,000: Preparation and filling of ophthalmics used for operation or cornea wound.
2. Autoclaves with adequate capacity fitting batch size shall he equipped with automatic
monitoring and recording devices.
3. Equipment, vessels, pipes, valves, pumps, etc that come into contact with solution shall he
made of high-quality materials resistant to corrosion. Pipe systems shall be constructed and
installed in a way to minimize joints. Filter and material for filter must not be absorptive to the
ingredients in solution or additive to solution. The use of asbestos-containing filters shall be fully
excluded.
4. Packaging materials that come into direct contact with products cannot be reused.
5. Principles for batch division:
(1) A batch of LVP or SVP means a specific quantity of the product which intended homogeneity
that is prepared in the same vessel at a time.
(2) A batch of powder for injection means a specific quantity of the product with intended
homogeneity that is produced with the same batch of active pharmaceutical ingredient in a single
continuous process cycle.
(3) A batch of lyophilized powder for injection is a homogenous product produced in the same
lyophilizer, with the same batch of solution in a manufacturing cycle.
6. Water for final washing of packaging materials that come into direct contact with products must
meet the requirements of water for injection.
7. Measures shall be taken to avoid re-contamination of materials, vessels, and equipment after
their final cleaning.
8. For packaging materials, equipment or others that come into direct contact with products, the
intervals between cleaning, drying, sterilization and their use shall be specified.
9. Intervals shall be provided between preparation of solution and sterilization or sterile filtration.
10. Materials, vessels, and equipment must be sterilized or disinfected before entering aseptic
operation areas.
11. Sampling of sterility test for finished product shall be conducted based on sterilization batch.
12. Active pharmaceutical ingredients and excipients should he separately stored on the basis of
the specifications and batch number. Each hatch shall he sampled and tested.
Chapter Ⅲ-Non-Sterile Pharmaceutical Products
Non-sterile pharmaceutical products refer to those for which sterility test is not included in official
specifications
1. The air cleanliness of production environment for non-sterile products is required as follows:
(1) Class 100,000:
Processing stages where oral liquid pharmaceuticals without final sterilization are exposed to;
Processing stages where topical pharmaceuticals for wound of deep tissue and the ophthalmics are
exposed to;
Processing stages where pharmaceuticals for cavity-medication are exposed to, except
pharmaceuticals for rectal medication.
(2) Class 300,000:
Processing stages where finally sterilized oral liquid pharmaceuticals are exposed to;
Processing stages where oral solid pharmaceuticals are exposed to;
Processing stages where pharmaceutical for dermal use are exposed to;
Processing stages where pharmaceutical for rectal medication are exposed to.
(3) The cleanliness of process for final handling of packaging materials, which come into direct
contact with products, shall be the same as that of corresponding products.
2. In cases where dust is significantly generated in clean room (area) and risks of
cross-contamination still exist even if dust-collecting equipment is installed, the air shall not be
recirculated by the air handling system.
3. For the rooms with the same cleanliness, the pressure of the operation room where dust is
significantly generated shall be relatively negative.
4. The exhaust air from air handling system for production of hormonal contraceptives shall be
treated harmlessly.
5. When the same equipment and air handling system have to be alternatively used for the
production of hormones, anti-neoplastic agents and other drugs, effective protection and cleaning
steps shall be taken and validated.
6. Filtration devices shall be installed at air-inlet of drying equipment and back flow prevention
devices shall be installed at air outlet.
7. Preparation and filling equipment as well as piping for ointment, ophthalmic ointment and
suppository shall be installed in a way to permit effective cleaning and disinfection.
8. Principles for batch division:
(1) A batch of solid or semi-solid preparations means a specific quantity of a product intended to
be homogeneous which is produced in the same mixer by a final mixing prior to molding or
filling.
(2) A batch of liquid preparations means a specific quantity of a product intended to be
homogeneous which is produced by final mixing prior to filling/sealing.
9.There shall be written procedures for purchase, acceptance, storage, maintenance, release and
discard of dies/punches that shall be kept by designated person in dedicated cabinet.
10. Ink to be directly printed on drug products shall meet requirements of food standards.
11. The utensils of easy breaking, shedding particles and mould generating shall be avoided in
production; when sieves used, special precautions shall be taken to prevent against contamination
by damaged sieves.
12. There shall be time limits for preparation, filtration, filling and sterilization of liquid products.
13. There shall be storage term and conditions for the intermediates of ointment, ophthalmic
ointment and suppository.
14. Water for preparation and final rinsing of equipment, utensils and packaging material having
direct contact with drug shall meet the specification of purified water.
Chapter Ⅳ-Active Pharmaceutical Ingredients
1. Personnel engaged in production of active pharmaceutical ingredients shall receive adequate
training in the knowledge relevant to the specific operations of such production.
2. Facilities for production and storage of inflammable, explosive, toxic and hazardous materials
shall be in compliance with the national regulations concerned.
3. Requirements of cleanliness class in refining, drying and packaging areas shall comply with the
following requirements:
(1) For active pharmaceutical ingredients whose sterility test is required according to the official
specifications, class 100 with a class 10,000 background shall be maintained in the area where the
product is exposed to.
(2) For others, class 300,000 or higher class shall he provided in the zone where the product is
exposed to.
4.In case that quality testing of intermediates interferes with the production environment, the
testing lab shall not be in such production area.
5.Hermetically sealed equipment is preferred for production of active pharmaceutical ingredients;
the sealed equipment and piping can be installed outdoors. Measures shall be taken to minimize
the risk of contamination whenever open equipment is applied or equipment is open for operation.
6.Materials or solvents received in large quantities shall be properly numbered when difficult to be
precisely divided by batch numbers, and the control systems covering their receipt, storage,
release and use shall be established, accordingly.
7.Manufacturers may determine the quality control items of the materials based on process
requirements, characteristics of the materials and suppliers' [BFQ][BF]audits.
8.There shall be procedures for approving the disposition of materials for special reasons, prior to
use. Release for use shall be subject to the person responsible for quality control.
9.Principles for batch division
(1) In the case of continuous processes, a divided fraction of active pharmaceutical ingredients
intended to be homogeneous within specified limits, and produced within a specified time interval.
(2) A divided quantity of active pharmaceutical ingredients produced in batches, and finally
blended to be homogeneous within specified limits. The product to be blended shall have been
produced with identical process and shall meet the quality specifications, with traceable records.
10. Production records for active pharmaceutical ingredients shall be traceable and batch
production records shall, at least, start from purifying of crude products. In the case of continuous
processes, the batch production records can be regarded as operation and quality control records at
different phases.
11. Non-conforming intermediates shall be clearly identified and prevented from entering next
process. Disposition of such products shall follow written procedures and be recorded.
12. Prior to the change from one product to another, the processing equipment shall be thoroughly
cleaned. In case of the successive processing with identical equipment for the same product, the
equipment shall also be cleaned to remove residue, if any, which adversely affects product quality,
when batch changes.
13. If cleaning of a specific type of equipment is difficult, the equipment may need to be dedicated
to the production and storage of particular intermediates or active pharmaceutical ingredients.
14. There shall be measures for preventing of mix-up and contamination of materials,
intermediates and active pharmaceutical ingredients in the course of movement within the building
or between buildings.
15. Water for purifying sterile active pharmaceutical ingredients and the final rinsing water for
packaging materials that come into direct contact with such ingredients shall conform to the
specifications of water for injection; water for purifying other ingredients shall meet the
specifications of purified water.
16. Control systems for preservation, use, rejuvenation and screening of strains for fermentation
shall be established and records shall be made.
17. Written procedures shall be followed to clean the containers allowed to be recirculated, and to
remove the previous labels.
18. Reserve samples shall be stored in the same containers as the products or in simulated market
containers, and under conditions consistent with product labeling.
Examination shall be performed in compliance with the established program.
Chapter Ⅴ-Biological Products
1. All personnel (including those concerned with cleaning and maintenance) engaged in the
manufacture of biological products shall be trained in appropriate fields (such as hygiene and
microbiology as well as safety protection), based upon the products being manufactured and the
production operation to be conducted.
2. The persons in charge of production and quality control shall possess relevant scientific
knowledge (bacteriology, virology, biology, molecular biology, biochemistry, immunology,
medicine and pharmaceutical science). They shall have sufficient practical experience to enable
them to exercise their management function for process concerned.
3. The air cleanliness of the production environment for biological products is required as follows:
(1) Class 100:
Formulation, pooling, filling/sealing, lyophilization, stoppering, and addition of stabilizer,
adjuvant and inactivation agent of the products with no sterile filtration before filling.
(2) Class 10,000:
Formulation, pooling, purification, addition of stabilizer, adjuvant and inactivation agent, sterile
filtration and ultrafiltration of the products to be strictly filtered before filling;
Filling of reactive sera and antigens/antibodies of diagnostic reagents in vitro.
(3) Class 100,000:
Plasma pooling, fractionation not at low temperature, pasteurization before filling, capping and
final rinsing of product containers;
Fermentation with closed system for oral preparations (aseptic manipulation is required under
unavoidably exposed conditions);
Coating, formulation, filling, and drying of ELLSLA reagents:
Production of reagents of gold colloidal test, PCR, paper-strip reagents and other diagnostic
reagents in vitro;
Formulation and filling of the products used for deep tissue trauma and extensive surface wound.
4. The air cleaning system and facilities shall comply with specific requirements in cases that
high-risk pathogens are handled for the production of different products.
5. Dedicated equipment shall he utilized in the stage of production when some specific live
organisms are handled, and it shall be conducted in a segregated area or in a closed system.
6. Production facilities for BCG and tuberculin shall be separated strictly from other production
premises, and dedicated equipment shall be used.
7. Spore-forming organisms shall be handled in facilities dedicated to this group of products until
the inactivation process is accomplished. For Bacillus anthracis, Clostridium botulinum and
Clostridium tetani dedicated facilities shall be utilized for each individual product.
8. Dedicated equipment shall be used for production of spore-forming organisms and a campaign
production of each individual product shall he carried out. Where the manufacture of
spore-forming organisms occurs in a facility or suite of facilities, only one product shall be
processed at a specified time.
9. Potential contamination to raw materials, final bulk and finished products, caused by facilities
and equipment, during the production of biological products shall be taken into consideration.
10. Segregated facilities shall be used for the production and testing of individual PCR reagent to
prevent the cross-contamination caused by aerosol generation during amplification.
11. When positive samples are handled during the production of HIV diagnostic reagents,
protective measures complying with related regulations shall be taken and dedicated facilities
must be used.
12. Seed lots and cell banks used for the production of biological products shall he stored in a
designated storeroom under appropriate conditions. Access to these areas shall be restricted to
authorized personnel.
13. Dedicated equipment shall be used for the production of the products derived from human
blood or plasma or animal organs and tissues, and the production area shall be separated strictly
from others.
14. Simultaneous production in the same area using closed systems of biofermentors may be
acceptable for products such as monoclonal antibodies and products prepared by recombinant
DNA techniques.
15. Products such as killed vaccines, including those made by rDNA techniques, toxoids, and
bacterial extracts after inactivation shall be dispensed into containers on the same premised or by
using the same filling and lyophilization equipment as other sterile biological products, providing
that adequate decontamination measures are taken after filling, including, if appropriate,
sterilization and washing. However, effective cleaning and disinfection shall be conducted after
filling of each product. The effectiveness of cleaning and disinfection shall he validated regularly.
16. Pathogenic microorganisms shall be handled within specifically designed areas under negative
pressures.
17. Air cleaning system shall be dedicated to the processing areas for handling live bacteria/virus
or killed bacteria/virus. Air from operation areas for pathogens shall not be recirculated and, in the
cases of organisms in a group above Risk Group 2, shall be exhausted through sterilizing filters
that are regularly checked for performance.
18. When infectious materials of the organisms in a group above Risk Group 2 are used for
production, effective decontamination systems shall be available for effluent.
19. The production area and equipment specialized for handling live organisms shall permit easy
cleaning and decontamination, and be resistant to fumigation.
20. Animals used for the production or quality control of biological products shall be
accommodated in separate premises from production areas. The requirements for animal breeding
and care shall comply with the regulations for laboratory animal management.
21. Water for injection for prodution shall be used up within 6 hours after preparation, or within 72
hours if sterilized within 4 hours after preparation, or it can be stored at 80℃ or above, or not
more than 4℃, or maintained by constant circulation at 65℃or above.
22. Pipework, valves and air-vent filters shall be properly designed to facilitate cleaning and
sterilization. The closed containers (such as fermentors) shall be completely steam-sterilizable.
23. The materials and apparatus contaminated by pathogens during the production process shall be
placed separately from sterilized materials and apparatus, and attached with clear labels.
24. Main raw materials used for production of biological products (including source plasma) shall
comply with the quality standards. They shall be tested and released by the quality control
department based upon satisfactory results.
25. The materials used for the production of biological products shall be purchased from the
approved suppliers. To assure the quality and stability of the supplied materials, contracts shall be
signed between purchasers and suppliers on the basis of assessment.
26. Detailed records shall be made when starting materials originated from animals are employed.
The records shall include, but not limited to, the source of animals, the conditions for animal
breeding and care and the health status of animals. The animals used for vaccine production shall
at least be of those above the Class of Clean Animals.
27. The seed lot system for production, e.g. primary seed lot, master seed lot and working seed lot,
shall be established. The records of seed lot system shall include its origin, characteristics, passage
history, demonstration of the organism from a single pure colony, features of production and
cultivation, its optimal storage conditions, etc.
28. The cell bank system for production including primary cell bank, master cell bank and
working cell bank shall be established. The records of cell bank system shall include the origin of
cells (including karyology analysis and tumorigenicity), population doublings, passage history,
demonstration of cells from a pure cell line preparation method, optimal storage conditions, etc.
29. All personnel engaged in production, maintenance, testing and animal care, and inspectors
shall be vaccinated with appropriate vaccines and shall receive the regular health examination.
30. The personnel subject to any infectious diseases or conditions, skin diseases or wounds, and
those with potential risk to adversely affect the quality of products shall be precluded from
working in the production area or from conducting tests.
31. To sanitize clean areas for the production of biological products and the areas where necessary,
more than one way shall be selected for disinfection, and changed regularly, and the tests should
be conducted so as to prevent the development of resistant strain of organisms.
32. When the production dealing with infectious agents such as cholera, plague, HIV and HBV, etc
is accomplished, the suspected contaminates shall be sterilized in situ and individually before they
are removed from the working area.
33. During the working day, personnel shall not pass the way from areas where live
microorganism or animals are handled, if no defined decontamination measures are taken, to
premises where other products or organisms are handled. Persons not concerned with the
production process shall not enter the production area except for essential purposes and in those
cases they shall wear sterile protective clothing.
34. The staff engaged in production processes shall be separated from those responsible for animal
care.
35. Manufacture of biological products shall be performed by strictly following the Chinese
Requirements for Biological Products or the production processes approved by the State Drug
Administration.
36. Starting materials, starting liquid semi-products and finished products of biological products
shall be tested by following strictly the Chinese Requirements for Biological Products, or the
quality standards approved by the State Drug Administration.
37. The production batch of biological products shall be divided in accordance with the
Requirements for the Division of Production Batch as described in the Chinese Requirements for
Biological Products, and the batch number shall be given accordingly.
38. The national biological standard substances shall be prepared, calibrated and distributed by the
National Quality Control Laboratory for Drug and Biological Products. Manufacturers shall
prepare their own working standards with the reference of the national biological standards.
39. The quality control department shall be independent from production management department,
and directly report to the top managers of the manufacturer. The quality control department shall
take the responsibilities of supervision regarding to raw materials, equipment and product quality,
sales and adverse reaction. Release of a finished product shall be conditional on satisfactory
results obtained from the tests of in-process and final quality control.
Chapter Ⅵ-Radioactive Pharmaceuticals
1. The top management responsible for supervision of production and quality management, and
the heads of the production and quality management department shall possess the qualification of
nuclear medicine & radioactive pharmaceuticals (RPhs) and have adequate experience in the RPhs
production and quality management.
2. The personnel engaged in RPhs quality control shall be trained and certified in the test of RPhs.
3. The personnel engaged in RPhs production shall be trained and certified in production
technique & radiation protection.
4. There shall be a radiation protection department in a manufacturer, whose main responsibilities
are as follows:
(1) To assure that radiation protection regulations are implemented, and education and training are
performed;
(2) To conduct surveillance of the radiation protection.
(3) To report to the authorities concerned promptly in case radiation accident occurs, and to assist
in the investigation and handling.
5. Premises shall comply with the national regulations on the radiation protection. The
manufacturer shall be licensed for operating radioisotopes.
6. The cleanliness in the RPhs production area shall meet the specified requirements for sterile,
non-sterile products and active pharmaceutical ingredients respectively. The ingredients of
radioimmunoassay (RIA) kits shall be prepared in Class 300,000.
7. The floor, work desk for operating radionuclides shall be made with the materials that can be
decontaminated easily. To operate radioactive iodine and other volatile radionuclides shall be in
ventilation hood whose specifications comply with the national regulations concerned.
8. The production areas for RPhs with different nuclides must be strictly separated. The working
areas of radioactivity and non-radioactivity shall be effectively segregated.
There shall be monitoring zone surrounding contamination source. Detection shall be conducted
regularly.
9. There shall be change rooms with shower for decontamination at entrance and exit of
production area, and a detector for radioactive contamination at the exit.
10. For storing radioactive materials, there shall be a safe and convenient site with clear symbol of
radiation. Facilities for prevention from fire, stealing and leakage shall be available in compliance
with the requirements of radiation protection.
11. Dedicated decontamination room shall be designed and constructed for recovering the packing
containers for radioactive materials.
12. Other facilities suited to the need of production and quality management shall be provided.
13. Radionuclides or standard radiation sources shall be stored in a dedicated storage or cabinet,
and be kept by designated persons with special records.
14. Labels shall be printed in accordance with special rule for RPhs.
15. Outer packaging materials for RPhs shall comply with the national regulations of radiation
protection.
16. The contamination level of body surface and clothes of RPhs operators, and equipment, wall,
and floor in working area shall comply with the national regulations concerned.
17. RPhs operators shall have protective suit, including coverall, work cap, gloves and respirator
as required. Other articles for protection, such as shoes, socks and additional coveralls shall be
available for working area of high or moderate radio activities.
Operators shall wear gauze mask of high efficiency at the site likely contaminated by radioactive
gas or vapor; Gas mask, compressed air respirators and plastic overall-shirt shall be provided
under the condition of severe pollution.
18. The coveralls of RPhs operators shall be checked for contamination before washing,
contaminated coveralls shall be disposed specially or handled as radioactive waste.
19. Contaminated area shall be specially decontaminated under supervision of persons responsible
for radiation protection. The area cannot be used until passing examinations.
20. There shall be containers for radioactive waste in the radioactive working area and the waste
shall be disposed according to the national regulations concerned.
21. There shall be taken measures to reduce radioactivity in liquid and gas wastes prior to
discharging. The acceptance level of the waste shall comply with the national regulations.
22. Validation shall be carried out according to the general requirements of the annex with
additional validation items including radiation protection, exhaust hood, and disposition of liquid
and gas wastes.
23. There shall be batch records, which include batch production records, batch packaging records,
batch test records, etc.
24. There shall be written procedures for storage, requisition, use and return of radionuclides. The
records shall be made.
25. There shall be written procedures for supervision and inspection for radiation protection and
records shall be made.
26. There shall be written procedures for disposition of radioactive liquid, gas and solid wastes
and records shall be made.
27. Both inner and outer packages are used for RPhs; the outer package shall be attached with a
label, and a RPhs symbol and an insert sheet; the inner package shall be with a label.
28. For purpose of transportation, the used empty container of RPhs and radionuclide shall be
packed and monitored for radiation dose according to the national regulations concerned, and the
records shall be made.
29. Appropriate protection devices shall be provided for the package and transportation of RPhs
against radiation dose.
30. Safety for radiation protection of RPhs shall be checked before delivery
31. There shall be special vehicle for instant labeling RPhs.
32. It shall be reported immediately to local drug regulatory agencies when hazard to patients
occurs by over dose of radioactivity.
Chapter Ⅶ-Preparations of Traditional Chinese Medicines
1. The personnel responsible for production and quality management shall possess the technical
knowledge of Traditional Chinese Medicines (TCM);
2. The persons responsible for check of receiving Chinese crude drugs and their prepared slices
shall possess the skill as to identify and recognize authentic and sham, and quality grades.
3. Doors and windows of premises for producing external preparations for non-traumatic surface
and some specific preparations shall be closed as required. Facilities for dehumidification,
ventilation, dust collection and cooling shall be equipped where needed. The requirements for
flows of personnel and materials, and operations refer to those for clean rooms (areas) in the
Provisions.
The premises for dispensing, crushing, mixing and screening of cleaned crude drugs and dry
extracts used for formulation directly shall be well closed, with facilities for ventilation and dust
collection. The requirements for flows of personnel and materials, and operations shall refer to
those for clean rooms (areas) in the Provisions.
Cleanliness of production environment for other TCM preparations shall be in conformity with the
requirements for non-sterile and sterile products, accordingly.
4. There shall be separate rooms in a warehouse for raw and cleaned materials of Chinese crude
drugs. Toxic and precious crude drugs shall be stored in dedicated rooms or containers
respectively.
5. The interior surfaces of premises, such as floors, walls and ceilings, without cleanliness
requirements shall be smooth, easy to clean, free from cracks and moulds. It shall prevent products
from contamination.
6. Workbenches for sorting and selecting of Chinese crude drugs shall be available in the premises
for cleaned crude drugs. The surface of a workbench shall be flat and non-additive.
7. Premises for processing, such as steaming, parching, stir-flying and calcining of Chinese crude
drugs, shall suit to production capacity, and be equipped with ventilation, de-fuming, dust
collection, and cooling facilities.
8. Premises for extraction and concentration of crude drugs or their prepared slices shall suit to
production capacity, and be equipped with ventilators and facilities to prevent against
contamination and cross-contamination.
9. Equipment shall be available to permit dust collection in the area for sorting, cutting and
crushing processes of crude drugs.
10. Tools and containers that come into direct contact with products shall be of smooth surfaces,
easy to clean and disinfect and shall not be additive.
11. Certificates of analysis issued by port drug quality control laboratory shall be available for
importing Chinese crude drugs and their prepared slices.
12. Purchased Chinese crude drugs and their prepared slices shall have records and details of data.
Each package unit shall bear clear labels specifying the name of items, specifications, quantity,
origin, and date of collecting (processing). Toxic, explosive, and flammable crude materials shall
be properly marked.
13. Sorting, trimming, cutting, washing, processing, etc. of Chinese crude drugs shall follow the
instructions prior to formulation. Soaking process shall ensure that the material is fully saturated
without extra water.
14. Chinese crude drugs and their prepared slices shall be stored and maintained properly to assure
the quality.
15. Principles of batch division
(1) Divided quantity of a solid preparation intended to be homogeneous, and molded and packed
with materials blended in the same mixer and in a single process. In the case of multi-mixing, a
divided quantity of products intended to be homogeneous within specified limits, if validated.
(2) Divided quantity of a liquid preparation, soft extract, extract, or liquid extract intended to be
homogeneous, finally mixed in the same mixer prior to filling/sealing.
16. Precious and toxic materials or their prepared slices for production shall be dispensed under
control according to the established procedure, and documented.
17. The following measures shall be taken for preventing against cross-contamination or mix-ups
in production:
(1) Chinese crude drugs shall not be directly contacted with the ground.
(2) Special precautions against cross-contamination shall be taken in the operations of toxic crude
drugs.
(3) Flowing water shall be used for washing of sorted crude drugs. Used water is not allowed to
wash other crude drugs. Different crude drugs shall not be washed together.
(4) Washed and cut crude drugs, and processed preparations shall not be dried in the open air.
18. Sterilization for Chinese crude drugs, intermediates and finished products shall not affect the
quality.
19. Processing water used for washing, soaking and extracting of Chinese crude drugs and their
prepared slices shall meet the quality standards of drinking water.