( MOH Decree No. 79 )
The Good Manufacturing Practice for Drugs (2010 Revision), adopted at
the executive meeting of the Ministry of Health on October 19, 2010, is
hereby promulgated and shall go into effect as of March 1, 2011.
Minister of MOH
January 17, 2011
Good Manufacturing Practice (GMP) for Drugs
Chapter 1 General Provisions
Article 1: These provisions of Good Manufacturing Practice
(GMP) for Drugs, in accordance with the Drug Administration Law of the
People’s Republic of China and the Regulations for Implementation of the
Drug Administration Law of the People’s Republic of China, are enacted
to regulate the manufacturing and quality management of Drugs.
Article 2: The manufacturer should establish a quality management
system. The system should cover all factors that influence the quality
of drugs, including all organized and planned activities with the
objective of ensuring that the drugs are of the quality required for
their intended use.
Article 3: GMP, as part of the quality management system, is the basic
requirement of production and quality control of drugs, to ensure the
products are consistently manufactured in accordance with the
registration requirements, and are suitable for their intended use, by
minimizing the risks of contamination, cross-contamination and mixups or
errors in manufacturing process.
Article 4: The manufacturer should strictly implement GMP with
integrity. Any falsification and fraud is forbidden.
Chapter 2 Quality Management
Section 1 Principle
Article 5: The manufacturer should establish a quality objective to meet
quality management requirements so that all registration requirements
related to drug safety, efficacy and quality are systematically
implemented throughout the entire process of production, control,
product release, storage and distribution, to ensure that the products
are manufactured in accordance with the registration requirements, and
are suitable for their intended use.
Article 6: The attainment of the quality objective is the responsibility
of senior management and requires the participation and commitment by
staff at all levels within the manufacturer, by the manufacturer’s
suppliers and by the distributors.
Article 7: The manufacturer should be adequately resourced with
competent personnel, suitable and sufficient premises, equipment and
facilities for achieving its quality objective.
Section 2 Quality Assurance
Article 8: Quality Assurance is a part of the quality management system.
The manufacturer should establish the Quality Assurance system with the
support of a complete documentation system to ensure its effective
Article 9: The system of Quality Assurance should ensure that:
1. Drugs are designed and developed in a way that takes account of the
requirements of GMP.
2. Production and quality control operations are in compliance with GMP.
3. Managerial responsibilities are clearly specified.
4. Arrangements are made for the purchase and use of the correct
starting and packaging materials.
5. All necessary controls on intermediate products are effectively
6. Qualifications and validations are carried out.
7. Drugs are correctly processed, checked, tested, and verified,
according to the defined procedures.
8. Each batch of products is not released before the approval of the
9. Satisfactory arrangements exist to ensure that the drugs are stored,
distributed and subsequently handled.
10. Self-inspection is regularly carried out to appraise the
effectiveness and applicability of the Quality Assurance system,
according to the procedures.
Article 10: The basic requirements of production and quality control are
1. All manufacturing processes are clearly defined, systematically
reviewed and shown to be capable of consistently manufacturing drugs of
the required quality and complying with their specifications.
2. Steps of manufacturing processes and significant changes to the
process are validated.
3. All necessary resources are provided including:
1) Appropriately qualified and trained personnel;
2) Adequate premises and space;
3) Suitable equipment and services;
4) Correct starting materials, packaging materials and labels;
5) Approved master manufacturing documents and operation procedures;
6) Suitable storage and transport.
4. Instructions and procedures are written in clear and unambiguous
5. Operators are trained to carry out procedures correctly.
6. Records should be made during the entire manufacture and any
deviations are investigated and recorded accordingly.
7. Records of manufacture and distribution, which enable the complete
history of a batch to be traced, are retained in a comprehensible and
8. The distribution of the products minimizes any risk to their quality.
9. A system is available to recall any batch of product, from sale or
10. Complaints about marketed products are examined, the causes of
quality defects investigated and appropriate measures taken in respect
of the defective products and to prevent reoccurrence.
Section 3 Quality Control
Article 11: Quality Control is concerned with organization and
documentation, and with sampling, testing and etc., which ensure that
the necessary tests are actually carried out and that materials or
products are not released, until their quality has been judged to be
Article 12: The basic requirements of Quality Control are that:
1. Adequate facilities, equipment, instruments and trained personnel are
resourced, to ensure the related quality control activities are done
effectively and reliably.
2. Approved procedures are available for sampling, inspection and
testing starting materials, packaging materials, intermediate, bulk, and
finished products, and stability study, and where appropriate for
monitoring environmental conditions, to ensure the compliance with GMP.
3. Samples of starting materials, packaging materials, intermediate,
bulk and finished products are taken by authorized personnel with
4. Testing methods are validated or verified.
5. Records are made for sampling, inspecting and testing. Any deviations
are investigated and recorded.
6. Records are made of the results of inspection and that testing of
materials, intermediate, bulk, and finished products is formally
assessed against specification.
7. Sufficient reference samples of starting materials and finished
products are retained to permit future inspection and testing of the
product when necessary, and that the finished product is retained in its
final package unless exceptionally large packages are produced.
Section 4 Quality Risk Management
Article 13: Quality risk management is a systematic process for the
assessment, control, communication and review of the risk to quality
throughout the entire product life cycle. It can be applied both
proactively and retrospectively.
Article 14: The evaluation of the risk to quality is based on scientific
knowledge and experience, to ensure the quality of products.
Article 15: The level of effort, formality and documentation of the
quality risk management process is commensurate with the level of risk.
Chapter 3 Organization and Personnel
Section 1 Principle
Article 16: The manufacturer should establish a management structure and
have an organization chart. The quality management department should be
independent from other departments to carry out responsibilities of
Quality Assurance and Quality Control. The quality management department
can be structured into the quality assurance department and the quality
control department separately.
Article 17: The quality management department should participate in all
quality related activities, and review all GMP related documents. The
responsibilities of quality management personnel are not permitted to be
delegated to personnel of other departments.
Article 18: The manufacturer should have an adequate number of
managerial and operating personnel with appropriate qualifications (with
respect to, including education, training, and practical experience).
The responsibilities of each department and each position should be
clearly specified. There should be no gaps or unexplained overlaps in
the responsibilities. The responsibilities placed on any one individual
should not be extensive.
All personnel should be fully aware of and understand their
responsibilities, be familiar with related requirements, and receive
necessary training, including initial training and continuing training.
Article 19: Duties normally should not be delegated to other personnel.
If deemed necessary, the duties can only be delegated to designated
deputies of a satisfactory qualification level.
Section 2 Key Personnel
Article 20: Key posts should be occupied by full-time personnel, which
should at least include the heads of the manufacturer, production
management, quality management, and the Qualified Person.
The heads of production and quality management must be independent from
each other. The head of the quality management and the Qualified Person
can be the same person. Procedures should be established to ensure the
independence of the Qualified Person for fulfilling responsibilities,
without interference from the head of the manufacturer or other
Article 21: The head of the manufacturer
The head of the manufacturer is principally liable for product quality
and routine operation. In order to achieve the manufacturer’s quality
objective and compliance with GMP, the head of the manufacturer should
provide necessary resources, make appropriate plan, organization and
coordination, and ensure that the quality management department can
fulfill its responsibilities independently.
Article 22: The head of production management
1. Qualification: The head of production management should, at a
minimum, possess a college degree in pharmaceutical or relevant
specialties (or with an intermediate professional technique certificate
or a pharmacist’s license), with at least three years of practical
experience in pharmaceutical production and quality management, among
which at least one year in production management, with necessary
training relating to the products being manufactured.
2. Main responsibilities:
1) To ensure that products are produced and stored according to approved
master manufacturing documents in order to obtain the required quality;
2) To ensure strict implementation of the procedures relating to
3) To ensure that the batch records of processing and packaging are
evaluated and signed by a designated person before they are sent to the
quality management department;
4) To ensure that the premises and equipment are maintained and serviced
to function in a sound operating state;
5) To ensure that the necessary validations are done;
6) To ensure that required initial and continuing training of personnel
in production is carried out and adapted according to need.
Article 23: The head of quality management
1. Qualification: The head of the quality management should, at a
minimum, possess a college degree in pharmaceutical or relevant
specialties (or with an intermediate professional technique certificate
or a pharmacist’s license), with at least five years of practical
experience in pharmaceutical production and quality management, among
which at least one year in quality management, with necessary training
relating to the products being manufactured.
2. Main responsibilities:
1) To ensure that all starting materials, packaging materials,
intermediate, bulk and finished products meet the registration
requirements and specifications;
2) To ensure that the batch records are reviewed before product release;
3) To ensure that all necessary testing is carried out;
4) To approve specifications, sampling instructions, testing methods and
other quality management procedures;
5) To review and approve all quality related changes;
6) To ensure all significant deviations and out-of-specification results
are timely investigated and handled;
7) To approve and monitor any contract analysis;
8) To check the maintenance of premises and equipment for the purpose of
maintaining a sound operating state;
9) To ensure the necessary qualifications or validations are done
appropriately, and to review and approve validation protocols and
10) To ensure self-inspection is done;
11) To assess and approve material suppliers;
12) To ensure all quality related complaints are timely and properly
investigated and handled;
13) To ensure the implementation of on-going stability study and make
the stability data available;
14) To ensure that the product quality reviews are done;
15) To ensure that the necessary initial and continuing training of
personnel in Quality Control and Quality Assurance is carried out and
adapted according to need.
Article 24: The heads of production and quality management generally
have some shared, or jointly exercised, responsibilities relating to
1. The review and approval of master manufacturing documents,
2. The monitoring of manufacturing environment and plant hygiene;
3. Ensuring the critical equipment has been qualified;
4. Ensuring the completion of manufacturing process validation;
5. Ensuring the required initial and continuing training of all related
personnel of the manufacturer is carried out and adapted according to
6. The approval and monitoring of contract manufacturers;
7. The designation and monitoring of storage conditions for materials
8. The retention of records;
9. The monitoring of compliance with GMP;
10. The monitoring of the factors that may affect product quality.
Article 25: Qualified Person
1. Qualification: The Qualified Person should, at a minimum, possess a
college degree in pharmaceutical or relevant specialties (or with an
intermediate professional technique certificate or a pharmacist’s
license), with at least five years of practical experience in
pharmaceutical production and quality management, with work experience
in in-process control and quality testing.
The Qualified Person should possess necessary theoretical knowledge in
relevant specialties，be trained in product release so as to fulfill its
2. Main responsibilities:
1) To participate in quality management activities such as establishment
of the quality system, self-inspection, external quality audit,
validation, adverse drug reaction reporting and product recalls;
2) To be responsible for product release and to ensure that the
production and testing of each batch of released products are in
accordance with the related regulations, the registration requirements
3) Prior to the release of each batch, the Qualified Person must issue a
review record for product release according to the requirements in the
above paragraph 2, and archive it to the batch record.
Section 3 Training
Article 26: The manufacturer should designate a specific department or
person(s) to take charge of training activities. A training program and
plan reviewed or approved by the head of production management or
quality management should be available. Training records should be
Article 27: Training should be provided for all personnel in production
and quality activities. The content of the training should be
appropriate to the responsibilities assigned to them. Besides the
training on the theory and practice of the Provisions, there should be
training on relevant laws and regulations, and job related
responsibilities and skills. The practical effectiveness of the training
should be periodically assessed.
Article 28: Personnel working in high-risk areas (e.g. production areas
for highly active, toxic, infectious or sensitizing materials) should be
given specific training.
Section 4 Personnel Hygiene
Article 29: All personnel should receive training of hygiene
requirements. The manufacturer should establish personnel hygiene
operation procedures to minimize the risks of contamination in drug
production caused by personnel.
Article 30: The personnel hygiene operation procedures should include
contents relating to the health, hygiene practices and clothing of
personnel. Every person whose duties take him into the production and
quality control areas should correctly understand and follow these
procedures. The manufacturer should take measures to ensure the
implementation of these procedures.
Article 31: The manufacturer should have management on the employee’s
health and establish health archives. Personnel engaged in manufacturing
who is in direct contact with drugs should receive medical examination
before being assigned to work, and the examination should be carried out
at least annually afterward.
Article 32: The manufacturer should take measures to ensure that no
person having open lesions on the exposed surface of the body, affected
by an infectious disease or other diseases that may contaminate the
products, is engaged in the manufacture of drugs.
Article 33: Visitors or untrained personnel should, preferably, not be
taken into the production and quality control areas. If this is
unavoidable, they should be given information in advance, particularly
about personal hygiene and the prescribed protective clothing.
Article 34: Every person entering manufacturing areas should wear
protective garments as required. The material and style of garments, and
way of gowning should be appropriate to the specific work conducted, and
the required air cleanliness level.
Article 35: Persons entering clean areas should not wear make-up,
jewelry or similar accessories.
Article 36: In production and storage areas, smoking or eating and
drinking, or the storage of food, drink, cigarettes or personal
medication, as well as other goods not for manufacturing should be
Article 37: Direct contact should be avoided between the operator’s
hands and the exposed product, immediate packaging materials, as well as
with any part of the equipment that comes into contact with the
Chapter4 Premises and Facilities
Section 1 Principle
Article 38: The location, design, lay-out, construction, adaption and
maintenance of premises should suit the drug production requirements,
and should minimize the risk of contamination, cross-contamination,
mixups and errors, as well as permit effective cleaning, operation and
Article 39: Premises should be situated in an environment that, when
considered together with measures to protect the manufacturing process,
presents minimal risk of causing contamination of materials or products.
Article 40: The manufacturer should have a neat manufacturing
environment. The ground, roads, and transportation in plant area should
not introduce contamination to the manufacturing. The general layout of
production, administration, living and ancillary areas should be well
designed to avoid interference from each other. Premises and buildings
should be well designed to ensure the logical flow of materials and
Article 41: Premises should be carefully maintained, ensuring that
repair and maintenance operations do not present any hazard to the
quality of products. They should be cleaned and, where applicable,
disinfected according to detailed written procedures.
Article 42: Lighting, temperature, humidity and ventilation should be
appropriate and such that they do not adversely affect, directly or
indirectly, either the product quality during their manufacture and
storage, or the accurate functioning of equipment.
Article 43: Premises and facilities should be designed and equipped so
as to afford maximum protection against the entry of insects or other
animals. Necessary measures should be taken to avoid the contamination
to equipment, materials and products caused by raticide, insecticide,
fumigation reagent, etc.
Article 44: Measures should be taken in order to prevent the entry of
unauthorized people. Production, storage and quality control areas
should not be used as a right of way by personnel who do not work in
Article 45: Drawings of premises, facilities and the fixed pipes should
be archived as built or after modification.
Section 2 Production Area
Article 46: In order to minimize the risks of contamination and
cross-contamination, premises, facilities and equipment should be
designed, laid out and used appropriately in accordance with the
properties of the manufactured product and its process, as well as the
corresponding cleanliness level, and the following requirements should
1. A comprehensive consideration of the aspects such as properties of
products, processes and intended uses etc. should be given, so as to
determine the feasibility of sharing premises, facilities and equipment
for different products, along with an assessment reports.
2. Dedicated and self-contained premises, facilities and equipment must
be used for the production of products with particular properties such
as highly sensitizing products (e.g. penicillins) or biological
preparations (e.g. Bacillus Calmette Guerin vaccine or any other
products derived from live microorganisms). Dust generating operation
areas in penicillin production should maintain relatively negative
pressure, the exhaust air should be decontaminated as required, and the
air outlet should be far away from the air inlet of other air-handling
3. Dedicated facilities (e.g. a dedicated air handling system) and
equipment must be used in production of β-lactam products and sex
hormonal contraceptives, and their production areas must be strictly
segregated from those of other products.
4. Dedicated facilities (e.g. a dedicated air handling system) and
equipment should be used for some hormonal, cytotoxic and highly potent
chemical products. In exceptional cases, the principle of campaign
working in the same facilities and equipment can be accepted provided
that specific precautions are taken and the necessary validations are
5. The exhaust air from the air handling system in above paragraphs 2, 3
and 4 should be decontaminated;
6. The production of non-drugs with adverse effects on drug should not
be allowed in premises used for drugs.
Article 47: The adequacy of the production area and storage area should
ensure the orderly positioning of equipment, materials, intermediate,
bulk and finished products, so as to avoid mixups, cross-contamination
between different products and materials, and to avoid the omissions or
errors of any of the manufacturing or quality control steps.
Article 48: Production areas should be effectively ventilated, with air
control facilities (including temperature, humidity and filtration)
appropriate to the products handled, the operations undertaken within
them and the external environment, to ensure that the production
environment is in accordance with the requirements.
The air pressure differential between clean and non-clean areas, or
between differently classified clean areas should not be less than 10Pa.
When necessary, an appropriately-graded pressure differential should be
maintained between rooms of different functions (operation rooms) with
the same cleanliness level.
The exposed processing areas for oral liquid and solid preparations,
drugs applied through tract (including recta), epidermal products, and
other non-sterile products, as well as the exposed processing areas for
handling immediate packaging materials should be designed as Grade D
according to requirements in Annex 1 of GMP for sterile products. The
manufacturer may take appropriate measures to monitor the microorganism,
in accordance with product specifications and property.
Article 49: Interior surfaces (walls, floors and ceilings) of a clean
area should be smooth, free from cracks, open joints and dust retention,
and should not shed particulate matter, and should permit easy and
effective cleaning and, if necessary, disinfection.
Article 50: Pipes, light fittings, ventilation points and other services
should be designed and sited to avoid the creation of recesses that are
difficult to clean. As far as possible, they should be accessible from
outside the manufacturing areas for maintenance.
Article 51: Drains should be of adequate size, and have trapped gullies.
Open channels should be avoided where possible, but when unavoidable,
shallow channel are recommended to facilitate cleaning and disinfection.
Article 52: Weighing of starting materials for preparations usually
should be carried out in a separate weighing room designed for that use.
Article 53: Operation areas where dust is generated (e.g. during
sampling, weighing, mixing and packaging of dry materials and products)
should be kept under relatively negative pressure, and specific measures
should be taken to avoid dust diffusion and cross-contamination, and to
Article 54: Premises or areas for the packaging of drugs should be
reasonably designed and laid out, so as to avoid mixups or
cross-contamination. Where several packaging lines are in the same area,
there should be segregation in place.
Article 55: Production areas should be well lit, particularly where
visual on-line controls are carried out.
Article 56: In-process controls areas may be set up within the
production area without bringing any risk to product quality.
Section 3 Storage Areas
Article 57: Storage areas should be of sufficient capacity to allow
orderly storage of the various categories of materials and products:
starting and packaging materials, intermediate, bulk and finished
products, products in quarantine, released, rejected, returned or
Article 58: Storage areas should be designed or constructed to ensure
good storage conditions, with ventilation and lighting facilities. Where
special storage conditions (e.g. temperature, humidity, light shade) and
security are required, these should be provided, checked and monitored.
Article 59: Highly active materials or products and printed packaging
materials should be stored in safe and secure areas.
Article 60: Receiving, dispatch and distribution bays should protect
materials and products from the weather (e.g. raining, snowing).
Reception areas should be designed and equipped to allow containers of
incoming materials to be cleaned where necessary before storage.
Article 61: Where a separate area is needed for the storage of materials
in quarantine, the area must be clearly marked and its access restricted
to authorized personnel.
Segregation should be provided for the storage of rejected, recalled or
returned materials or products.
Any system replacing the physical quarantine should give equivalent
Article 62: There should normally be a separate sampling area for
materials, which air-cleanliness levels should be the same as the
corresponding production area. If sampling is performed in other areas
or with other methods, it should be conducted in such a way as to
prevent contamination or cross-contamination.
Section 4 Quality Control Areas
Article 63: Quality Control laboratories usually should be separated
from production areas. Laboratories for the control of biological,
microbiological and radioisotopes should also be separated from each
Article 64: Laboratories should be designed to suit its intended use and
avoid mixups and cross-contamination. There should be adequate space for
samples handling, storage of retention and stability samples, and
storage of records.
Article 65: Separate rooms may be necessary to protect sensitive
instruments from vibration, electrical interference, humidity, or
interference of other external factors.
Article 66: Regulatory requirements should be met in laboratories
handling particular substances, such as biological or radioactive
Article 67: Experimental animal houses should be well isolated from
other areas, and their design and construction should comply with
relevant regulatory requirements. There should be dedicated air handling
facilities and separate entrance for animal access.
Section 5 Ancillary Areas
Article 68: Rest and refreshment rooms should not bring any hazard to
production, storage and quality control areas.
Article 69: Facilities for changing clothes and for washing and toilet
purposes should be easily accessible and appropriate for the number of
users. Toilets should not communicate directly with production or
Article 70: Maintenance workshops should as far as possible be separated
from production areas. Whenever parts and tools are stored in the clean
area, they should be kept in rooms or lockers reserved for that use.
Chapter 5 Equipment
Section 1 Principle
Article 71: The design, selection, installation, adaption and
maintenance of equipment should be suitable for its intended use,
minimize the risk of contamination, cross-contamination, mixups or
errors, and facilitate operation, cleaning, maintenance, as well as
disinfection or sterilization if necessary.
Article 72: Procedures for the use, cleaning, maintenance and repair of
the equipment should be established, and their operation records should
Article 73: The documents and records for equipment procurement,
installation, and qualification should be archived.
Section 2 Design and Installation
Article 74: Production equipment should not present any hazard to drug
quality. The surface of the production equipment that come into direct
contact with the drug should be smooth, spotless, and easy to clean,
disinfect, sterilize and anti-corrosive. It must not be reactive,
additive or absorptive to affect product quality.
Article 75: Weighing, measuring equipment, instruments and gauges of an
appropriate range and precision should be available.
Article 76: Appropriate washing and cleaning equipment should be chosen
and used in order not to be a source of contamination.
Article 77: Lubricant and refrigerant etc. used in the equipment should
not contaminate products or containers. Food grade or equivalent
lubricant should be used whenever possible.
Article 78: Procedures for purchase, check and acceptance, storage,
maintenance, dispensing and discarding of the production molds should be
established. The molds should be kept by designated personnel in
dedicated cabinets and recorded accordingly.
Section 3 Maintenance and Repair
Article 79: Repair and maintenance operations should not present any
hazard to product quality.
Article 80: Preventive maintenance plans and procedures should be
established, and the maintenance and repair activities should be
Article 81: Equipment that has undergone change or major repair should
not be put into use until it is re-qualified.
Section 4 Usage and Cleaning
Article 82: Clear operating procedures should be available for major
items of production and test equipment.
Article 83: Production equipment should be operated within qualified
Article 84: Production equipment should be cleaned according to detailed
Operation procedures for the cleaning of production equipment should
specify a detailed and complete cleaning method, equipment and tools for
cleaning, names and preparation methods of detergents, methods of
removing identification marks of the previous batch, methods of
protecting cleaned equipment from contamination prior to use, the
maximum storage time after cleaning, and methods of checking the
cleanliness status of equipment before use, so as to enable operators to
clean the equipment in a reproducible and effective manner.
Where equipment needs to be disassembled, sequence and methods for
disassembling and reassembling of equipment need to be set up. Where
equipment needs to be disinfected or sterilized, methods for
disinfecting or sterilizing, name of the detergent and its preparation
need to be included in the procedures. The maximum intervals between the
completion of production and cleaning of equipment should also be
specified when necessary.
Article 85: Production equipment after cleaning should be stored in a
clean and dry condition.
Article 86: Log books should be established for equipment and
instruments used for drug production and testing, to record the use,
cleaning, maintenance and repair activities, along with the date, time,
and the name, strength ,batch number, etc., of the drug produced and
Article 87: Production equipment should be clearly labeled to indicate
the equipment reference number and the contents (e.g. product name,
strength, batch number, etc.). The equipment without contents should be
labeled to indicate its cleaning status.
Article 88: Defective equipment should, if possible, be removed from
production and quality control areas, or at least be clearly labeled as
Article 89: Main fixed pipes should be clearly labeled to indicate the
contents and the direction of flow.
Section 5 Calibration
Article 90: Weighing and measuring equipment, gauges, recording and
control equipment and all instruments used in production and testing
should be calibrated and checked at defined intervals according to the
operation procedures and calibration plans, and related records should
be retained. Calibration should cover the range used in production and
Article 91: Key weighing, measuring equipment, gauges, recording and
control equipment used in production and testing should be calibrated to
ensure that data readout is accurate and reliable.
Article 92: Calibration should be done with standard measuring
instruments meeting regulatory requirements. Calibration records should
include the name, code, calibration validity date and number of
accreditation certificate to ensure their traceability.
Article 93: Weighing and measuring equipment, gauges, recording and
control equipment should be clearly labeled to indicate the calibration
Article 94: Weighing and measuring equipment, gauges, recording and
control equipment which are not calibrated or beyond the shelf life or
inaccurate should not be used.
Article 95: Automated or electronic equipment used in production,
packaging and storage should be regularly calibrated and checked
according to procedures, in order to ensure their proper functioning.
Calibration and checks should be recorded accordingly.
Section 6 Water for Pharmaceutical Use
Article 96: Water for pharmaceutical use should be suitable for its
intended use, and meet the specifications of the Chinese Pharmacopeia
and the related requirements. It should at least be sourced from
Article 97: Water treatment plants and distribution systems should be
designed, constructed, operated and maintained so as to ensure that
water for pharmaceutical use meets the defined specifications. They
should not be operated beyond their designed capacity.
Article 98: The materials of storage tanks and pipes for transport of
purified water and water for injection should be non-toxical and
corrosion resistant. The vent of storage tanks should be installed with
non-fiber releasing hydrophobic microorganism retention filter. Dead
legs should be avoided in the design and installation of pipelines.
Article 99: Purified water and water for injection should be produced,
stored and distributed in a manner that prevents microbial growth.
Purified water can be circulated, and water for injection can be
circulated at a temperature above 70℃.
Article 100: The quality of water for pharmaceutical use and its water
sources should be monitored at defined intervals, and recorded
Article 101: The pipes for purified water and water for injection should
be cleaned and sanitized according to operation procedures and recorded
accordingly. If bioburden of water for pharmaceutical use exceeds alert
or action limits, actions should be taken according to operation
Chapter 6 Materials and Products
Section 1 Principle
Article 102: Starting materials and immediate packaging materials used
for drug production should meet the required specifications. Ink printed
directly on drug should meet the food grade requirements.
Imported starting materials should comply with importation regulations.
Article 103: Operation procedures for handling and managing materials
and products should be established to ensure the proper receiving,
storage, dispensing, use and distribution of materials and products, to
prevent any risk of contamination, cross-contamination, mixups and
All handling of materials and products should be carried out according
to operation procedures and master manufacturing documents, and recorded
Article 104: Quality assessment should be performed for the
determination and change of material suppliers, and procurement can only
be carried out after the suppliers have been approved by quality
Article 105: Materials and products should be transported in a manner to
protect their quality. Where special requirements are needed, the
transportation conditions should be verified.
Article 106: The operation procedures should be established for the
receipt of each delivery of starting materials and immediate and printed
packaging materials. All incoming materials should be checked to ensure
that the delivery corresponds to the purchase order, and is from a
supplier that has been approved by the quality management department.
Outer packages of materials should be labeled with the required
information, and cleaned where necessary. Damage to outer packages or
any other problem that might adversely affect the quality of materials
should be reported to the quality management department, investigated,
Each receipt should be recorded, including:
1. The name of the material on the delivery note and the containers;
2. The "in-house" name and/or code of material;
3. The date of receipt;
4. The name of the supplier, and of the producer if different;
5. The batch number of the supplier, and of the producer if different;
6. The total quantity, and number of containers received;
7. The batch number or serial number assigned after receipt;
8. Any relevant comment (e.g. state of the containers).
Article 107: Incoming materials and finished products should be
quarantined immediately after receipt or processing, until they are
released for use or distribution.
Article 108: All materials and products should be stored in an orderly
fashion according to their nature, to permit batch segregation and stock
rotation. Their dispensing and distribution should comply with the
principle of first-in-first-out and first-expiry-first-out.
Article 109: Where computerized storage systems are used, operation
procedures should be in place to prevent mixups and errors of materials
and products in cases of system malfunction or outage, etc.
Where fully computerized storage systems are used for identification,
the information of materials and products may not be necessarily labeled
in a written form.
Section 2 Starting Materials
Article 110: Appropriate operation procedures should be established,
defining proper measures such as checking or testing, to verify the
correctness of the identity of starting materials in each package.
Article 111: If one material delivery is made up of different batches,
each batch must be considered as separate for sampling, testing and
Article 112: Starting materials in the storage area should be
appropriately labeled. Labels should bear at least the following
1. The designated name and the internal code reference of the material;
2. A batch number given at receipt;
3. The quality status of the contents (e.g. in quarantine, released,
4. The shelf life or re-test date.
Article 113: Only starting materials which have been approved to release
by the quality management department and which are within their shelf
life or re-test date should be used.
Article 114: The storage of starting materials should be in accordance
with the expiry or re-test date. Re-test should be carried out for
materials within the shelf life in case of encountering any abnormal
situations that may adversely affect the quality of materials.
Article 115: Dispensing should only be carried out by designated
personnel according to operation procedures. After being checked,
materials should be accurately weighed or measured, and well labeled.
Article 116: Each dispensed material and its weight or volume should be
independently checked by another person, and the check recorded.
Article 117: Materials dispensed for each batch should be kept together
and conspicuously labeled as such.
Section 3 Intermediate and Bulk Products
Article 118: Intermediate and bulk products should be kept under
Article 119: Intermediate and bulk products should be clearly labeled,
including at least the following information:
1. The name of the product and the internal code reference;
2. The batch number;
3. Quantity or weight (e.g. gross weight, net weight);
4. Process steps (if necessary);
5. The quality status of the product (e.g. in quarantine, released,
rejected and sampled, if necessary).
Section 4 Packaging Materials
Article 120: The requirements for management and control of immediate
and printed packaging materials should be the same as for starting
Article 121: Packaging materials should be issued for use only by
designated personnel according to operation procedures. Measures should
be taken to prevent mixups and errors to ensure the correct use of
packaging materials for drug production.
Article 122: Procedures for the design, review and approval of printed
packaging materials should be established to ensure the contents printed
are in line with what is approved by drug regulatory department. .
Specific documents should be established, to store the original specimen
of printed packaging materials approved with signature.
Article 123: When the version of a printed packaging material is
changed, actions should be taken to ensure that the correct version is
used for production. It is recommended that the obsolete stencil plates
be withdrawn and destroyed.
Article 124: Printed packaging materials should be properly stored in
specific area so as to exclude unauthorized access. Cut labels and other
loose printed packaging materials should be stored and transported in
separate closed containers so as to avoid mixups.
Article 125: Printed packaging materials should be kept by designated
person and dispensed according to operation procedures and requests.
Article 126: Each delivery or batch of immediate or printed packaging
materials should be given a specific reference number or identification
mark, indicating product name and batch number.
Article 127: Outdated or obsolete printed packaging materials should be
destroyed and its disposal recorded.
Section 5 Finished Products
Article 128: Finished products should be held in quarantine until
Article 129: Finished products should be stored under conditions in
accordance with the approved specifications of drug registration.
Section 6 Controlled Materials and Products
Article 130: Check and acceptance, storage and managing of narcotics,
psychotropic, and medicinal toxic drugs (including traditional Chinese
medicinal materials) for medical use, radioactive drugs, pharmaceutical
precursor chemicals, flammable and explosive materials and other
dangerous goods should strictly follow government regulations.
Section 7 Others
Article 131: Each packaging container of rejected materials,
intermediate, bulk and finished products should be clearly marked, and
properly stored in restricted areas.
Article 132: The handling of rejected materials, intermediate, bulk and
finished products should be approved by head of quality management, and
Article 133: The recovery should be authorized beforehand. This recovery
should be carried out after a thorough evaluation of the quality risks
involved, and recorded accordingly. The shelf life of the recovered
product should start from the date when its earliest batch is produced.
Article 134: The reworking of finished preparations is prohibited. The
rejected intermediate, bulk and finished preparations usually should not
be reprocessed. Reprocessing is only permitted if the quality of the
final product is not affected, the specifications are met, and that it
is done according to a predefined and approved operation procedure after
a thorough evaluation of the risks involved. The reprocessing should be
Article 135: The need for additional testing and stability test of any
finished product that has been reprocessed, reworked or into which a
recovered product has been incorporated, should be considered by the
quality management department.
Article 136: The manufacturer should establish operation procedures for
handling returned products with related records including at least: the
product name, batch number, strength, quantity, return entity and
address, reasons and date for return and final decision.
The returned products of the same batch but from different distributors
should be recorded, stored and disposed separately.
Article 137: Returned products may be considered for re-packaging or
re-distribution for sale only after checking, testing and investigation
so as to prove with evidence that their quality is not adversely
affected, and after assessment by the quality management department
according to operation procedures. At minimum, the following factors
such as nature of the drug product, required storage conditions, its
current condition and history, and the time elapsed since it was
distributed, should be taken into account in this assessment. The
returned product not complying with the storage and transport
requirement should be destroyed under supervision of the quality
management department. Where any doubt arises over the quality of the
returned product, it should not be re-distributed.
Where the returned product is to be recovered, the recovered product
should meet both the defined specifications and requirements in Article
Any action taken and the outcome should be appropriately recorded.
Chapter 7 Qualification and Validation
Article 138: The manufacturer should identify what
qualification or validation work is needed, to prove that the critical
attributes of the operations can be controlled effectively. The scope
and extent of qualification or validation should be determined through
Article 139: The premises, facilities, equipment and testing instruments
should be qualified. The validated manufacturing process, operation
procedures and testing methods should be used for production, operation
and testing, and this validated state should be maintained.
Article 140: Documents and records should be established for
qualification and validation as an evidence for the following intended
1. Design qualification is to verify that the design of the premises,
facilities and equipment is suitable for the intended use and in
compliance with the Provisions;
2. Installation qualification is to verify that the premises, facilities
and equipment have been built and installed in accordance with their
3. Operational qualification is to verify that the premises, facilities
and equipment operate in accordance with their design specifications;
4. Performance qualification is to verify that the premises, facilities
and equipment, under normal operating procedures and process conditions,
can consistently meet performance specifications;
5. Process validation is to verify that a manufacturing process,
operated within established parameters, can consistently produce
products that are suitable for their intended use and in accordance with
the registration requirements.
Article 141: Before any new manufacturing formula or process is adopted,
its suitability for routine production should be validated. The
manufacturing process by using the defined starting materials and
equipment, should consistently produce products suitable for their
intended use and in accordance with the registration requirements.
Article 142: Qualification or validation should be performed when there
is a change in major factors influencing the product quality, including
any change in starting materials, immediate packaging materials,
production equipment and environment (or premises), manufacturing
process or testing method, etc. Where necessary, the changes should be
approved by drug regulatory departments.
Article 143: Cleaning validation should be performed in order to confirm
the effectiveness of a cleaning procedure, to effectively prevent
contamination and cross-contamination. In cleaning validation, a
comprehensive consideration should include factors such as the use of
the equipment, the detergents and disinfectants used, the sampling
methods and locations, the relevant recovery rate of sampling, the
nature and limit of residues, and the sensitivity of the testing method
Article 144: Qualification and validation should not be considered as a
one time activity. After initial qualification and validation,
requalification or revalidation should be carried out according to the
product quality review. Critical manufacturing processes and operation
procedures should be revalidated at defined intervals to ensure the
Article 145: The manufacturer should make a validation master plan to
document the key information of qualification and validation.
Article 146: Requirements should be defined in the validation master
plan or other relevant documents to maintain the consistent status of
premises, facilities, equipment, testing instruments, process, operation
procedures and testing methods.
Article 147: The qualification or validation protocol should be prepared
based on its object. The protocol should be reviewed and approved.
Responsibilities should be specified in the protocol.
Article 148: Qualification or validation should be implemented in
accordance with a predefined and approved protocol, and be recorded.
Upon completion of qualification or validation, a report should be
prepared, reviewed and approved. The qualification or validation result
and conclusion (including comments and suggestions) should be recorded
Article 149: Master manufacturing documents and operation procedures
should be established according to the validation results.
Chapter 8 Documentation Management
Section 1 Principle
Article 150: Documentation constitutes an essential part of the quality
assurance system. The manufacturer should have error-free written
documents of specifications, manufacturing formula, processing
instruction, operation procedures, records and etc.
Article 151: Manufacturer should establish operation procedures for
documentation management to systematically design, prepare, review,
approve and distribute the documents. Documents related to the
Provisions should be reviewed by the quality management department.
Article 152: The content of documents should comply with the requirement
of the drug manufacturing license, the registration requirements and
etc, to facilitate the tracing of batch history.
Article 153: Operation procedures should be followed for drafting,
revision, review, approval, replacement or withdrawal, reproduction,
storage and destruction of documents; and relevant records for
distribution, withdrawal, reproduction and destruction of documents
should be in place.
Article 154: The drafting, revision, review and approval of documents
should be signed and dated by appropriate personnel.
Article 155: Document should have title, nature, purpose, document
number and version number. The text should be definitive, clear,
understandable and unambiguous.
Article 156: Documents should be laid out in an orderly fashion and be
easy to check.
Article 157: The reproduction of master documents must not introduce any
error. Reproduced documents should be clear and legible.
Article 158: Documents should be regularly reviewed and revised. When a
document has been revised, systems should exist to prevent inadvertent
use of superseded documents. Distributed documents in use should be the
approved current version. Those superseded and outdated documents should
not be accessible in operating area except for archiving.
Article 159: Records should be made at the time each activity related to
the Provisions is taken and in such a way that activities concerning the
manufacture, quality control and quality assurance of products are
traceable. Sufficient space should be provided for data entering in the
record. The record should be entered timely and truthfully, and the
handwriting should be clear, legible and indelible.
Article 160: When collecting records, graphs, plots, etc., those printed
out from the production equipments and testing instruments should be
adopted where possible, and the product or sample name, batch number,
equipment information should be recorded along with the operator’s dated
Article 161: Records should be kept in a neat fashion without tearing up
or uncontrolled alteration. Any alteration made to the entry on a
document should be signed and dated; the alteration should permit the
reading of the original information. Where appropriate, the reason for
the alteration should be recorded. When transcription is needed, the
original record should not be destroyed, and be kept as attachment of
the transcribed record instead.
Article 162: Each batch of drug should have a batch record, which
includes related records of processing, packaging, testing, release, and
etc. This batch record should be retained for at least one year after
the product shelf life by the quality management department. Important
documents such as specifications, master manufacturing documents,
operation procedures, and the reports of stability study, qualification,
validation and changes should be retained for long term.
Article 163: Where data are to be recorded by electronic data processing
systems, photographic technique or other reliable means, operation
procedures related to the system should be available; and the accuracy
of the records should be checked.
If documentation is handled by electronic data processing methods, only
authorized persons should be able to enter or modify data in the system
and there should be a record of changes and deletions; access should be
restricted by passwords or other means and the entry of critical data
should be independently checked.
Batch records stored electronically should be protected by back-up
transfer on magnetic tape, microfilm, paper or other means. It is
particularly important that the data are safe, and readily available
throughout the period of retention.
Section 2 Specifications
Article 164: There should be appropriately authorized and dated
specifications for materials and finished products; where appropriate,
they should be also available for intermediate or bulk products.
Article 165: Specifications for materials should include, if applicable:
1. Basic information of materials, including:
1) Name designated by the manufacturer and internal code reference;
2) The reference of specifications;
3) The approved suppliers;
4) A specimen or sample of printed packaging materials.
2. Sampling and testing procedures or references to relevant operation
3. Qualitative and quantitative requirements with acceptance limits;
4. Storage conditions and precautions;
5. The shelf life or re-test date.
Article 166: Specifications for intermediate and bulk products should be
available, if these are purchased or dispatched. If the test results of
the intermediate products are used for the evaluation of the finished
product, the specifications should be similar to those for finished
products, as appropriate.
Article 167: Specifications for finished products should include:
1. The designated name of the product and the code reference;
2. The reference to the formula (where applicable);
3. The strength, dosage form and package type;
4. Sampling and testing procedures or references to relevant operation
5. The qualitative and quantitative requirements, with acceptance
6. The storage conditions and precautions;
7. The shelf-life.
Section 3 Master Manufacturing Documents
Article 168: A master manufacturing document approved by the
manufacturer should exist for each batch size of every drug. A packaging
instruction should exist for every package type of different drug
strengths and dosage forms. The establishment of master manufacturing
documents should be based on the process approved at the time of
Article 169: Master manufacturing documents should not be changed
without authorization. When revision is needed, they should be revised,
reviewed and approved according to relevant operation procedures.
Article 170: The master manufacturing documents should at least include:
1. The Master Manufacturing Formula:
1) The name of the product, and its reference code;
2) A description of the dosage form, strength of the product, and batch
3) A list of all starting materials to be used, with the amount of each,
described using the designated name and a reference that is unique to
that material (mention should be made of any substance that may
disappear in the course of processing); When conversion between
measuring methods or units is needed, the calculation method should be
2. The Processing Instructions should include:
1) A statement of the processing location and the equipment to be used
(e.g. operation room’s location and reference number, cleanliness level,
necessary temperature and humidity requirements, equipment type and
2) The methods, or the reference of relevant procedures, to be used for
preparing the critical equipment (e.g. cleaning, assembling,
3) Detailed stepwise processing and process parameter instructions (e.g.
checks on materials, pretreatments, sequence for adding materials,
mixing times, temperatures);
4) The instructions for any in-process controls with their limits;
5) A statement of the expected final yield with the acceptable limits,
and of relevant intermediate yields, where applicable, and the methods
for reconciliation and acceptance limits;
6) The requirements for bulk storage of the products, including the
container, labeling and special storage conditions;
7) Any special precautions to be observed.
3. The packaging instructions should include:
1) The pack size expressed in terms of the number, weight or volume of
the product in the final container;
2) A complete list of all the packaging materials required for a
standard batch size, including name, quantities, sizes and types, with
the code or reference number relating to the specifications of each
3) An example or reproduction of the printed packaging materials and
specimens, indicating where to apply batch number references, and
shelf-life of the product;
4) Special precautions to be observed, including an examination of the
area and equipment in order to ascertain the line clearance before
packaging operations begin;
5) A description of the packaging operation, including any significant
subsidiary operations, any precaution for equipment to be used and
checks on packaging materials prior to use;
6) Details of in-process controls with instructions for sampling and
7) Methods for reconciliation and acceptance limits about bulk products
and printed packaging materials.
Section 4 Batch Processing Records
Article 171: A batch processing record should be kept for each batch of
product so that the production history and quality related status of
that batch can be traced.
Article 172: A batch processing record should be based on the relevant
parts of the currently approved master manufacturing documents. Such
records should be designed to avoid transcription errors. The record
should carry the product name, dosage form, strength and batch number on
Article 173: The master batch processing records should be reviewed and
approved by the heads of production and quality management. The
reproduction and issuance should be managed and recorded according to
operation procedures, and only one copy of reproduced master records can
be issued for the manufacture of each batch.
Article 174: During processing, each operation should be recorded
timely, and after the operation, the records should be confirmed, signed
and dated by the operation personnel.
Article 175: A batch processing record should include:
1. The product name, strength, batch number;
2. Dates and time of commencement, and of completion of intermediate
stages and production;
3. The signatures of the person responsible for each stage of
4. Signatures of the operator of different steps of production and,
where appropriate, of the person who checked each of these operations
5. The batch number and the quantities of each starting material
actually weighed (including the batch number and amount of any recovered
or reprocessed products added);
6. Any relevant processing operation or event, process parameters and
control limits, and the reference number of major equipment used;
7. A record of the results obtained from in-process controls and the
signatures of the person(s) carrying them out;
8. The amount of product obtained at different stages of manufacture,
and reconciliation when necessary;
9. Records on special problems or abnormal events, including detailed
description or investigation report for any deviation with signed
Section 5 Batch Packaging Record
Article 176: A batch packaging record should be kept for each batch or
part batch processed so that batch packaging operations and quality can
Article 177: A batch packaging record should be based on the relevant
parts of the Packaging Instructions, and avoid transcription errors. The
record should carry the product name, strength, package size and batch
number on every page.
Article 178: The batch packaging record should carry the batch number
and the quantity of bulk product, as well as the batch number and the
planned quantity of finished product. The requirements of review,
approval, reproducing and issuance of original blank batch packaging
record is the same as that of original blank batch processing record.
Article 179: During packaging, each operation should be recorded timely,
and after the operation, the records should be confirmed, signed and
dated by the operation personnel.
Article 180: The batch packaging record should include:
1. The product name, strength, package size, batch number, manufacturing
date and shelf life;
2. The date(s) and times of the packaging operations;
3. The signatures of the responsible person carrying out the packaging
4. The signatures of the operators of the different steps;
5. The name, batch number and actually used quantities of each kind of
6. Records of checks according to master manufacturing documents,
including the results of in-process controls;
7. Details of the packaging operations carried out, including reference
numbers to equipment and the packaging lines used;
8. Samples of printed packaging materials used, with printed batch
number, shelf life and other contents ; for printed packaging materials
that are inconvenient to archive together with the batch packaging
record, a reproduction bearing the abovementioned contents may be
9. Records on special problems or abnormal events, including detailed
description or investigation report for any deviation from master
manufacturing documents, with signed authorization;
10. The name and reference number of all printed packaging materials and
bulk product, quantities of the issued, used, destroyed or returned
products, the actual quantities and reconciliation.
Section 6 Operation Procedures and Records
Article 181: Operation procedures should include the title, code,
version number, issuing department, effective date, distribution list,
along with the dated signatures of author, reviewer and approver, the
title, content, and change history.
Article 182: Premises, equipment, materials, documents and records
should have codes (or reference numbers). Operation procedures should be
established for the numbering/coding system to ensure the uniqueness of
the codes (or reference numbers).
Article 183: There should be operation procedures and the associated
records of actions taken and conclusions reached for:
1. Qualification and validation;
2. Equipment assembly and calibration;
3. Maintenance, cleaning and sanitation of premises and equipment;
4. Personnel matters including training, clothing, hygiene;
5. Environmental monitoring;
6. Pest control;
7. Change control;
8. Deviation handling;
Chapter 9 Production Management
Section 1 Principle
Article 184: The production and packaging of all drugs should follow
approved manufacturing formula and processing instructions and operation
procedures with records retained, in order to ensure the drugs meet
defined quality specifications and conform to drug manufacturing
licensing and registration approval requirements.
Article 185: Operation procedures should be established to differentiate
production batches, and the differentiations of production batches
should achieve homogenous quality and property of the product within the
Article 186: Operation procedures should be established to determine the
manufacturing date and batch number. Each batch of product should have a
unique batch number. Unless stipulated in other regulations, the
manufacturing date should be no later than the commencing date of the
last blending operation for formulation or filling (sealing) of the
product. The packaging date of the product should not be used as its
Article 187: For each product batch, checks on yields and reconciliation
of quantities should be carried out to ensure that there are no
discrepancies outside of the acceptable limits. If a discrepancy is
found, investigations should be performed to find out the reason, and
the batch can only be released after it has been made clear that no
potential quality risks exist.
Article 188: Operations on different products should not be carried out
simultaneously in the same room unless there is no risk of mixups or
Article 189: At every stage of processing, products and materials should
be protected from microbial and other contamination.
Article 190: When working with dry materials or products, special
precautions should be taken to prevent the generation and dissemination
of dust. This applies particularly to the handling of highly active,
toxic or sensitizing materials or products.
Article 191: At all times during processing, containers of all
materials, intermediate or bulk products, major items of equipment, and
where appropriate rooms used should be labeled or otherwise identified
with an indication of the product or material being processed, its
strength and batch number. Where applicable, this indication should also
mention the stage of the manufacturing process.
Article 192: Labels applied to containers, equipment or facilities
should be clear, unambiguous and in the format approved by relevant
departments of the manufacturer. In addition to the wording on the
labels, different colors may be used to distinguish the status of these
items (e.g. quarantined, accepted, rejected, or cleaned.).
Article 193: Checks should be carried out to ensure that pipelines and
other pieces of equipment used for the transportation of products from
one area to another are connected in a correct manner.
Article 194: The line clearance should be carried out upon completion of
each batch production to ensure that no materials, products or documents
relevant to the batch are left over in the equipment and operation area.
The previous clearance should be checked prior to the commencement of
the subsequent batch.
Article 195: Any deviation from master manufacturing documents or
operation procedures should be avoided as far as possible. Once a
deviation occurs, operation procedures for deviation handling should be
Article 196: Access to production premises should be restricted to
Section 2 Prevention of Contamination and Cross-contamination in
Article 197: Measures should be taken to avoid, as far as possible,
contamination and cross-contamination during production, for example:
1. Production in segregated areas for different products;
2. Using campaign production;
3. Providing appropriate air-locks and air extraction; keep pressure
differentials between areas with different cleanliness levels;
4. Minimizing the risk of contamination caused by recirculation or
re-entry of untreated or insufficiently treated air;
5. Keeping dedicated protective clothing inside areas where products
with special risk of cross-contamination are processed;
6. Using cleaning and decontamination procedures that are validated or
of known effectiveness; where appropriate, testing the residue on the
surface direct contact with materials;
7. Using “closed systems” of production;
8. Drying equipment should have air filters in inlet, and devices to
prevent air back flow in outlet,
9. Utensils that are fragile, liable to shed particulate matter or go
moldy should be avoided in the production and cleaning operations. When
sieves are used, there should be measures against contamination caused
by breaking of sieves,
10. Processing steps such as preparation, filtration, filling/sealing
and sterilization of liquid products should be completed within the
defined time limits;
11. The shelf life and storage conditions should be established for
intermediate products of semi-solid preparations, such as ointments,
creams and gels, and of suppositories.
Article 198: Measures to prevent contamination and cross-contamination
should be checked regularly and evaluated for their suitability and
Section 3 Processing Operations
Article 199: Before any new production is started, the equipment and
work area should be checked to ensure that no product residues,
documents or materials not required for the current operation are left,
and the equipment is clean and ready to operate, and the check result
should be recorded accordingly.
Before the processing operation starts , the names, codes, batch numbers
and labeling of all materials and intermediate products should also be
checked , to guarantee that they are correct and in accordance with the
Article 200: Any in-process controls and necessary environmental
monitoring should be carried out and recorded.
Article 201: The line clearance must be carried out and recorded by the
operators upon completion of each stage of a production batch. The
record should include the number of the operating room, the name and
batch number of the product, the process step, the date of clearance,
the checklist and the results, the signatures of the person responsible
for the clearance and the verifier. The records should be incorporated
into the batch processing record.
Section 4 Packaging Operations
Article 202: Packaging operation procedures should specify the measures
to minimize the risk of contamination, cross-contamination, mixups or
Article 203: Before packaging, checks should be performed to ensure that
the work area, packaging lines, printing machines and other equipment
are clean or ready for use, and that they are free from any products and
documents left from the last batch, or materials not relating to the
packaging of this batch. The results should be recorded accordingly.
Article 204: Before the packaging operation, all packaging materials
drawn for use should also be checked for correctness, and the name,
strength, quantity, and quality status of bulk products and all
packaging materials should be checked to ensure the conformity with
master manufacturing documents.
Article 205: The name, strength, batch number and batch size of the
product being handled should be displayed at each packaging area or
Article 206: Appropriate segregation or other precautions to effectively
prevent contamination, cross-contamination or mixups should be adopted
if several packaging lines are working simultaneously.
Article 207: Containers for filling should be clean before filling.
Attention should be given to avoiding any contaminants such as glass
fragments and metal particles.
Article 208: Filling and sealing should be followed as quickly as
possible by labeling. If it is not the case, appropriate operation
procedures should be applied to ensure that no mixups or mislabeling can
Article 209: The printed information (e.g. batch number or shelf life)
of the separate printing or on-site printing during the packaging
operation should be checked to ensure its correctness, and the check
recorded. If printing by hand, the check frequency should be increased.
Article 210: Special care should be taken when using cut-labels and when
over-printing is carried out off-line, to avoid mixups.
Article 211: Checks should be carried out to ensure that any electronic
code readers, label counters or similar devices are functioning
correctly. Such checks should be recorded.
Article 212: Printed and embossed information on packaging materials
should be distinct and resistant to fading or erasing.
Article 213: In-process control of the product during packaging should
include at least the following information:
1. The appearance of the packages;
2. Whether the packages are complete;
3. Whether the products and packaging materials are correct;
4. Whether the printed information is correct;
5. The correct functioning of on-line monitors.
Samples taken away from the packaging line should not be returned to
prevent the products from mixups or contamination.
Article 214: Where repackage is needed for products due to unusual event
during packaging, special examination, investigation should be
conducted, and repackaging should be approved by authorized personnel.
Detailed record should be kept for the repackage operation.
Article 215: Any significant discrepancy, observed during reconciliation
of the amount of bulk products, printed packaging materials or finished
products, should be investigated. Finished products should not be
released without the investigation conclusion.
Article 216: Upon completion of a packaging operation, any unused
batch-coded packaging materials should be destroyed, and the destruction
recorded. An operation procedure should be followed if un-printed
packaging materials are returned to stock.
Chapter 10 Quality Control and Quality Assurance
Section 1 Management of Quality Control Laboratories
Article217: The personnel, facilities, and equipment in the quality
control laboratories should be appropriate to the tasks imposed by the
product nature and the scale of the manufacturing operations.
The use of contract laboratories, not applicable under normal
circumstances, in conformity with the principles of contract analysis
detailed in Chapter 11, can be accepted for particular reasons, but this
should be stated in the certificate of analysis.
Article 218: The head of quality control should have appropriate
qualifications and experience in managing laboratories and can manage
one or more control laboratories within the same manufacturer.
Article219: Testing technician in quality control laboratories should at
least have a relevant technical school or high school education, have
received job related practical training, and passed the examination.
Article220: Necessary reference books such as pharmacopeias and
standards spectrum, and primary reference substances such as reference
standards and reference substances, should be available in quality
Article 221: Documentation in the quality control laboratories should be
in accordance with the principles in Chapter 8 and meet the following
1. The quality control laboratories should at least have the following
2) Sampling operation procedures and records;
3) Testing operation procedures and records (including testing records
or laboratory notebooks);
4) Testing reports or certificates;
5) Operation procedures, records and reports of environmental
monitoring, where required;
6) Validation reports and records of testing methods, where applicable;
7) Operation procedures and records of the calibration of instruments,
and use, cleaning and maintenance of equipment.
2. Testing records of each batch of drug should cover testing records of
all the intermediate, bulk and finished products to ensure the testing
history of the batch is traceable.
3. For some kinds of data (e.g. testing results, environment monitoring
data, microorganism monitoring data of water for pharmaceutical use), it
is recommended that records be kept in a manner permitting trend
4. In addition to the information of the batch record, other original
data or records should be retained and readily available.
Article 222: Sampling should at least meet the following requirements:
1. Personnel of quality management department should have the authority
to access to production and storage areas for sampling and
2. The sampling process should be done in accordance with approved
operation procedures. Operation procedures should well describe:
1) Person(s) authorized to take samples;
2) The method of sampling;
3) The equipment to be used;
4) The amount of sample to be taken;
5) Instructions for sub-division of the sample;
6) The type and condition of the sample container to be used;
7) Handling and labeling of the remains after sampling and the samples;
8) Precautions of sampling, including preventive measures taken to
minimize risks in sampling process, especially for sterile materials or
hazardous materials, and precautions to prevent contamination and
cross-contamination in the sampling process;
9) The storage conditions;
10) The cleaning methods and storage requirements of sampling equipment.
3. The sampling method should be scientific and rational to ensure good
4. Reference samples should be representative of the batch of materials
or products from which they are taken. Other samples may also be taken
to monitor the most stressed part of a process (e.g. the beginning or
the end of a process).
5. Sample containers should bear a label indicating the information such
as sample name, batch number, date of sampling, containers from which
samples have been drawn, and person taking the sample.
6. Samples should be stored under prescribed storage conditions.
Article 223: The test of materials and products of various production
stages should at least meet the following requirements:
1. The manufacturer should ensure that full test is done according to
the registered testing methods.
2. Testing methods should be validated under any of the following
1) Adoption of a new testing method;
2) Change of testing methods;
3) Testing method adopted is not included in the Chinese Pharmacopoeia
or other official standards;
4) Other testing methods requested by regulations for validation.
3. The manufacturer should verify those testing methods that do not need
validation so as to ensure the accuracy and reliability of testing data.
4. Written operation procedures for testing should be in place to
specify testing methods, apparatus and instruments to be used, and the
content of the procedures should be consistent with the verified or
validated testing methods.
5. The test results obtained should be recorded in a traceable manner
and checked to make sure that they are consistent with each other. Any
calculations should be critically examined.
6. The test record should include at least the following content:
1) Name of the material or product, dosage form, strength, batch number
or shipping batch number, where appropriate, the name of the
manufacturer and/or supplier;
2) References to the relevant specifications and testing procedures;
3) Type and serial numbers of apparatus or instruments;
4) Preparation batch numbers of solutions and culture media, the source
and lot number of reference standards;
5) Related information of animals used for testing;
6) Testing process, including preparation of reference solution,
operation of individual tests, necessary data of environment temperature
7) Test results, including observations, calculations, spectrum or
plots, and reference to the No. of any certificate of analysis;
8) Dates of testing;
9) Dates and signatures of the persons who performed the testing;
10) Dates and signatures of the persons who verified the testing and the
7. All the in-process controls, including those made by manufacturing
personnel, should be performed according to methods approved by the
quality management department, and the results recorded;
8. Laboratory volumetric glassware, reagents, solutions, reference
standards and culture media should be tested;
9. Animals used for testing should, where appropriate, be inspected and
quarantined before use. They should be maintained and controlled in a
manner that meets the regulations of lab animal management. They should
be identified, and records should be maintained, showing the history of
Article 224: Operation procedures for investigation of testing results
out of specification should be established in quality control
laboratories. Any out of specification results must be fully
investigated following the operation procedures and recorded
Article 225: The reference samples are materials or products that are
being kept by the manufacturer according to the operation procedures for
quality traceability or investigation. Samples for product stability
study are not reference samples.
The following requirements should be met for reference samples:
1. The reference samples should be managed according to operation
2. The reference samples should be representative of the batch of
material or product from which they are taken.
3. Reference samples of finished products:
1) There should be reference samples for each batch. Where a batch is
packaged into several distinct packaging operations, at least one
reference sample should be taken from each individual packaging
2) The package of reference samples should be identical to the products
in the market. If the package of reference samples of active
pharmaceutical ingredients (API) cannot be the same as the form in the
market, a simulated package may be adopted.
3) The retained sample should consist of at least twice the quantity
necessary for full tests (excluding sterility and pyrogen test, etc.) in
specifications approved in drug registration.
4) The reference samples should be visually examined at least once a
year during storage period unless the visual examination will affect the
sample integrity. Any abnormality should be fully investigated and
corresponding actions should be taken.
5) Visual inspection of reference samples should be recorded.
6) Reference samples should be stored in conditions accordance with the
approved registration requirements for at least one year after the shelf
7) When drug manufacturing is ceased or a manufacturer closes down, the
reference samples should be transferred to an authorized storage site
and the local drug regulatory department should be informed so that they
can obtain the sample when necessary.
4. Reference samples of materials:
1) The samples should be retained for every batch of starting materials
and immediate packaging materials used for preparation. It is not
necessary to retain some immediate packaging materials (such as infusion
bottles) if the finished product has already been retained.
2) The samples of materials should be of a size at least sufficient to
perform the identification test.
3) Except for those less stable starting materials, reference samples of
starting materials (other than solvents, gases or water for
pharmaceutical use used in the manufacturing process) and immediate
packaging materials should be retained for at least two years after the
release of product. That period may be shortened if the shelf life of
the materials is shorter.
4) The reference samples of materials should be stored in defined
conditions, and air tightly sealed when necessary.
Article 226: The management of laboratory reagents, solutions, culture
media and test microorganisms should meet at least the following
1. Laboratory reagents and culture media should be purchased from
reliable suppliers, and when necessary, the supplier should be assessed.
2. There should be records for the receipt of laboratory reagents,
solutions and culture media, the date of receipt should be indicated on
the container where necessary.
3. The preparation, storage and use of the laboratory reagents,
solutions and culture media should follow the relevant requirements or
instructions. In special cases, the laboratory reagents should be
identified or tested upon reception or before use.
4. The batch number, preparation date, and name of the operator should
be indicated on the labels of solutions and prepared culture media, and
a preparation record (including sterilization) should be available. The
shelf life and special storage conditions of unstable laboratory
reagents, solutions and culture media should be indicated on the label.
For reference solutions and titration solutions, the latest
standardization date and calibration factor should be labeled, and the
standardization records should be available.
5. Test on suitability of prepared culture media should be performed and
documented. The records for use of culture media should be available.
6. Microorganisms required for relevant tests should be available. And
operation procedures for storage, subculture, use, and disposal of test
microorganisms should be established and recorded accordingly.
7. The test microorganism should be properly labeled with at least the
following information: name of microorganism, code, generation,
generation date/subculture date and operator.
8. The test microorganism should be stored according to the specified
storage conditions. The manner and period of storage should not have
adverse effects to the growth characteristics of the test microorganism.
Article 227: The management of the standard substances or reference
substances should meet at least the following requirements:
1. The standard substances or reference substances should be used and
stored under specified storage conditions.
2. The standard substances or reference substances should be properly
labeled with at least the following information: name, batch number,
data of preparation (if available), shelf life (if available), open
date, purity or titration, and storage condition.
3. Where in-house working standard substances or reference substances
are to be self-prepared, the manufacturer should establish
specifications of the working standards and operation procedures for the
preparation, identification, testing, approval and storage. Each lot of
in-house working standard substance or reference substance should be
standardized against an official standard substance or reference
substance, and shelf life established. In addition, the working standard
substances or reference substances s should be standardized regularly to
demonstrate that their potency or assay is stable within shelf life. The
process and result of the standardization should be recorded.
Section 2 Release of the Materials and Products
Article 228: Operation procedures for release of the materials and
products should be respectively established with well defined criteria
and responsibilities. Relevant records should be available.
Article 229: The following requirements should at least be met in
1. The quality assessment of the materials should at least include
checks of producers’ certificates of analysis, integrity and sealing of
packaging, and test result.
2. A clear conclusion should be given to the quality assessment of
materials, such as release, reject or other decisions.
3. The release of materials should be approved with signature by a
Article 230: The following requirements should at least be met in
1. Each batch of drugs, prior to release, should undergo quality
assessment, so as to ensure that the products and manufacturing comply
with the registration requirements and the Provisions, and the following
activities should be confirmed:
1) The main manufacturing processes and testing methods are validated.
2) All necessary inspections and tests are completed; the actual
production condition and record are considered comprehensively.
3) All the necessary production and quality control are completed and
signed by relevant responsible persons.
4) Changes are closed according to related procedures. Those needing
approval of the regulatory department are approved.
5) Required sampling, inspection, testing and review caused by changes
or deviations are completed.
6) Deviations related to this batch are clearly explained or
illustrated, or thoroughly investigated and appropriately handled; if
other batches are involved in the deviation, all batches should be dealt
2. Product quality assessment should have a clear conclusion, such as
release, reject or other decisions.
3. The release of each batch of products should be approved with
signature by the Qualified Person.
4. Lot release certificate should be obtained for vaccines, blood
products, in-vitro diagnostic reagents used in blood screening, and
other biological products stipulated by the State Food and Drug
Administration prior to final release.
Section 3 On-going Stability Program
Article 231: The purpose of the on-going stability program is to monitor
the product over its shelf life to permit the detection of any
manufacture related stability issue (e.g. changes in levels of
impurities or dissolution profile) , and to determine that the product
quality remains, and can be expected to remain, within specifications
under the labeled storage conditions.
Article 232: The on-going stability program mainly applies to the drug
in the package in which it is sold, but consideration should also be
given to the inclusion in the program of bulk product. For example, when
the bulk product is stored for a long period before being packaged
and/or shipped from a manufacturing site to a packaging site, the impact
on the stability of the packaged product should be evaluated and studied
under ambient conditions. In addition, consideration should be given to
intermediate products that are stored and used over prolonged periods.
Article 233: The on-going stability program should be described in a
protocol and results formalized as a report. The equipment used for the
on-going stability program (in particular, the equipment and facilities
for stability study) should be qualified and maintained following the
general rules of Chapters 7 and 5.
Article 234: The protocol for an on-going stability program should
extend to the end of the shelf life period and should at least include
the following contents:
1. Number of batch(es) per strength and different batch sizes;
2. Relevant physical, chemical, microbiological and biological testing
methods, with consideration of the specified stability study testing
3. Reference to testing methods;
4. Acceptance criteria;
5. Description of the container closure system(s);
6. Testing intervals (time points);
7. Conditions of storage (standardized conditions of Chinese
Pharmacopoeia for long term testing, consistent with the product
labeling, should be used);
8. Test items, if less than the quality specifications of a finished
product, it should be justified.
Article 235: The number of batches and frequency of testing should
provide a sufficient amount of data to allow trend analysis. Unless
otherwise justified, at least one batch per year of product manufactured
in every strength and every primary packaging type, should be included
in the stability program, unless none are produced during that year.
Article 236: In certain situations, additional batches should be
included in the on-going stability program. For example, an on-going
stability study should be conducted after any significant change or
significant deviation to the process or package. Besides, any reworking,
reprocessing or recovery batches should be also considered included in
the program, unless the validation and stability studies have been
Article 237: Results of on-going stability studies should be made
available to key personnel and, in particular, to the Authorized
Person(s). Where on-going stability studies are carried out at a site
other than the site of manufacture of the bulk or finished product,
there should be a written agreement between the parties concerned.
Results of on-going stability studies should be available at both sites
for review by regulatory authority.
Article 238: Out-of-specification results or significant atypical trends
should be investigated. Any confirmed out-of-specification result, or
significant negative trend, the manufacturer should consider the
possible impact on the marketed products. If necessary, a recall should
be carried out, and investigation result and actions taken should be
reported to the local drug regulatory department.
Article 239: A summary of all the data generated, including any interim
conclusions on the program, should be written and maintained. This
summary should be subjected to periodic review.
Section 4 Change Control
Article 240: The manufacturer should establish a change control system
to evaluate and manage all changes which could have an impact on product
quality. Any change requiring approval from the drug regulatory
department should only be applied after obtaining the approval.
Article 241: Operation procedures should be established to define the
request, assessment, review, approval and implementation of changes in
starting materials, packaging materials, specifications, testing
methods, operation procedures, premises, facilities, equipment,
instruments, manufacturing process and computer software. The quality
management department should assign a designated person to take charge
of the change control.
Article 242: For all changes, the potential impact on product quality
should be evaluated. The manufacturer should classify the changes (e.g.
major or minor) depending on their nature and extent, and the effects
these changes may impact on product quality. Scientific evidences should
be provided to determine what validation activities, additional tests
and stability studies are needed.
Article 243: Change that may affect the product quality is proposed by
an application department, steps should be taken to do assessment, and
then establish an implementation plan with defined responsibilities,
followed by its final review and approval by the quality management
department. The implementation of change should be fully recorded.
Article 244: When changes involve key quality factors such as starting
materials, immediate packaging materials, manufacturing process, major
equipment, etc., the quality of at least the first three batches
produced after the change should be evaluated. If the change has
potential impact on the shelf life, stability studies should also be
Article 245: When implementing changes, measures should be taken to
ensure that all documents affected by the changes are revised.
Article 246: All documents and records related to changes should be kept
by quality management department.
Section 5 Deviation Handling
Article 247: The head of each department should ensure that all
personnel of his department follow manufacturing process,
specifications, testing methods and operation procedures to prevent
Article 248: The manufacturer should establish operation procedures for
deviation handling, define the reporting, recording, investigation,
treatment and corrective actions adopted and all should be recorded
Article 249: The potential impact of any deviation on product quality
should be assessed. The manufacturer may classify the deviations (e.g.
as minor or major) depending on the nature and scope of the deviations
and extent of the potential impact on product quality. Additional tests
and impact on the shelf life should be considered for the assessment of
major deviations, and if necessary, stability studies should also be
carried out for products involved in major deviations.
Article 250: Any deviation from manufacturing process, material
reconciliation, specifications, testing methods and operation procedures
etc. should be recorded, and promptly reported to the person in charge
and the quality management department with a clear description. Full
investigation for major deviations should be carried out by the quality
management department in conjunction with other departments, and a
report should be filed. All deviation reports should be reviewed and
signed by the designated personnel of the quality management department.
The manufacturer should take preventive actions to effectively avoid the
re-occurrence of similar deviations.
Article 251: The quality management department should be responsible for
classifying deviations, and for the retention of all documents and
records related to investigation and handling of deviations.
Section 6 Corrective Actions and Preventive Actions
Article 252: The manufacturer should establish a corrective actions and
preventive actions (CAPA) system, for the investigation of complaints,
recalls, deviations, findings of self-inspections or external
inspections, process performances and quality monitoring trends, etc,
and take corrective actions and preventive actions. The extent and
formality of investigations should be commensurate with the level of
risk. The CAPA system should result in enhanced product and process
understanding, and product and process improvements.
Article 253: The manufacturer should establish operation procedures for
the implementation of CAPA, including at least the following:
1. To identify existing or potential quality issues by analyzing
complaints, recalls, deviations, findings of self-inspections or
external inspections, monitoring trends of process performance and
quality and quality data from other sources; when necessary, statistical
approaches should be employed;
2. To investigate causes related to the product, process and quality
3. To determine necessary CAPA measures for preventing issues from
4. To evaluate the applicability, effectiveness and sufficiency of CAPA
5. To record all changes during CAPA implementation;
6. To ensure that the related information is delivered to the Qualified
Person and the person directly in charge of preventing issues from
7. To ensure that the related information and its CAPA pass the review
by the senior management.
Article 254: CAPA implementation should be recorded and retained by the
quality management department.
Section 7 Supplier Assessment and Approval
Article 255: The quality management department should perform quality
assessment of all production materials suppliers, on-site audit to key
materials suppliers (especially the producers) in conjunction with other
departments, and exercise its veto against the suppliers who fails to
conform to the requirements of quality assessment.
The determination of key materials should comprehensively take into
account of the quality risk of the drugs produced by the manufacturer,
the materials consumption and the impact on product quality.
The legal person of the manufacturer, the head of the manufacturer and
other personnel should not interfere with or impede the independent
quality assessment performed by the quality management department for
Article 256: Operation procedures for assessment and approval of
materials suppliers should be established to define the suppliers’
qualifications, selection criteria, quality assessment methods,
assessment criteria, and approval procedures of material suppliers.
Where the quality assessment needs to be done by way of on-site quality
audit, the content and frequency of the audit, the composition and
qualifications of auditors should also be defined. Where small scale
pilot production is needed, the batch size, manufacturing processing
procedures, specifications, and stability study protocol should also be
Article 257: Designated person should be appointed by the quality
management department for supplier quality assessment and on-site
quality audit, as well as issuing the lists of approved suppliers. The
designated person should have relevant regulatory and technical
knowledge, and sufficient practical experiences in quality assessment
and on-site quality audit.
Article 258: The on-site quality audit should verify the authenticity of
the supplier’s qualification certificates and certificates of analysis,
and verify the testing conditions. In order to fully assess the quality
assurance system of the suppliers, its personnel and organization ,
premises, facilities, equipment, materials management, manufacturing
process procedures, production management, as well as the equipment,
instruments and documentation management, etc., of the quality control
laboratories should be checked. . An on-site audit report should be
Article 259: When necessary, small scale pilot production should be
carried out with the samples provided by key material suppliers, and the
stability study for the products from pilot production should be
Article 260: Assessment of material suppliers by the quality management
department should at least include: the supplier’s qualification
certificates, specifications and certificates of analysis, the
manufacturer’s testing data and reports of material samples. Where
on-site audit and small scale pilot production are performed, the
assessment should also include on-site audit report, certificates of
analysis and stability study report of small scale pilot products.
Article 261: Where changing a materials supplier, quality assessment
should be performed for the new supplier. Where changing a key material
supplier, validation and stability study for the product should be
Article262: Quality management department should distribute the list of
approved suppliers to material management department. The list should at
least include the names of materials, sizes/strengths, specifications,
names and addresses of the material producers, names of the distributers
(if any), etc., and be updated timely.
Article263: Quality management department should sign a quality
agreement with a key material supplier to define the quality
responsibilities of each party.
Article264: Quality management department should perform periodic
assessment or on-site quality audit for material supplier, retrospective
review of materials test results, records of quality complaints and
non-conformance handling. In case of occurrence of materials quality
problems, or significant changes of critical factors that may impact
quality, such as production conditions, manufacturing process,
specifications and testing methods, an on-site quality audit should be
performed as soon as possible.
Article265: The manufacturer should establish a quality archive for each
material supplier, which includes the supplier’s qualification
certificates, quality agreements, specifications, sample testing data
and reports, supplier’s certificates of analysis, on-site quality audit
reports, product stability study report, periodic quality review
Section 8 Product Quality Review
Article266: Quality review for each drug produced should be conducted
annually according to operation procedures, with the objective of
verifying the consistency of the existing processes, the appropriateness
of current specifications for both starting materials and finished
product, to highlight any adverse trends timely, and to identify product
and process improvements. Historical data from the previous such reviews
should be considered; internal audit should be carried out to confirm
the effectiveness of such reviews.
Quality reviews may be grouped by dosage forms, such as solid
preparations, liquid preparations, sterile products, and etc., where
Reports should be prepared after review.
Quality reviews performed by the manufacturer should include at least
1. All changes of starting materials used for the product, especially
those materials from new suppliers;
2. Critical in-process controls and testing results of finished product;
3. All batches that failed to meet the established specifications and
4. All significant deviations and related investigations, and the
effectiveness of corrective and preventative actions taken;
5. All changes of the process or testing methods;
6. Changes approved by or submitted to drug registration for the record;
7. The results of the stability program and any adverse trend;
8. All quality-related returns, complaints, recalls and the
9. The performance and adequacy of any corrective action taken for
product process or equipment;
10. The work accomplished according to post-marketing requirements of
registration for the drug newly approved and with changes;
11. The qualification status of relevant equipment and utilities, such
as HVAC, water, compressed gases, etc;
12. The fulfillment of technical agreements for contract manufacture or
Article 267: The result of quality review should be evaluated. An
assessment advice about whether corrective and preventative actions need
to be taken, or requalification or revalidation to be conducted, should
be raised and explanation provided. All these actions should be
completed in time and effectively.
Article 268: For contract manufacturing, a written technical agreement
should be in place between contract giver and contract acceptor, which
defines their respective responsibilities of the product quality review
to ensure that the quality review is performed on schedule according to
Section 9 Complaints and Adverse Drug Reaction Reports
Article 269: Adverse drug reactions (ADRs) reporting and monitoring
system should be established, and managed by a specific organization
staffed with specialized personnel.
Article 270: The ADRs should be actively collected, recorded in detail,
evaluated, investigated, and handled. Actions should be taken timely to
control any potential risk. ADRs should be reported to the regulatory
department as required.
Article 271: Operation procedures should be established to define the
process of recording, evaluating, investigating, and handling of
complaints. The measures for a complaint due to a possible product
defect should also be defined. Consideration of the necessity of a
recall from the market should be included.
Article 272: There should be designated person(s) supported by
sufficient staff for investigating and handling of the quality
complaints, and the Qualified Person should be made aware of any
complaints and investigations.
Article 273: All the complaints should be recorded and reviewed. Any
complaint concerning a product quality defect should be recorded with
all the original details and thoroughly investigated.
Article 274: If a product defect is discovered or suspected in one
batch, consideration should be given to checking other batches in order
to determine whether they are also affected.
Article 275: Investigation and handling of a complaint should be
recorded, and product information of related batches should also be
Article 276: Complaint records should be reviewed regularly, in order to
find problems which require attention, occur repeatedly, and possibly
need a recall of drugs from the market. Actions should be taken
Article 277: The manufacturer should take actions timely for
manufacturing failure, drug deterioration, or any other serious quality
problems. If necessary, actions taken should be reported to the local
drug regulatory department.
Chapter 11 Contract Manufacture and Analysis
Section 1 Principle
Article 278: To ensure the product quality of contract manufacture, and
the accuracy and reliability of contract analysis, there must be a
written contract between the contract giver and the contract acceptor,
which clearly establishes the duties of each party, and covers the
manufacture and/or analysis arranged under contract and any technical
arrangements made in connection with it.
Article 279: All arrangements for contract manufacture and analysis
including any proposed changes in technical or other arrangements should
be in accordance with the drug manufacturing licensing and registration
requirements for the product concerned.
Section 2 The Contract Giver
Article 280: The contract giver is responsible for assessing the
contract acceptor, via on-site audit of the conditions, technical levels
and quality management status, to confirm its competence to carry out
the contracted operations, and to ensure the compliance with the
Article281: The contract giver should provide the contract acceptor with
all the information necessary to carry out the contracted operations
correctly in accordance with the drug registration and any other
The contract giver should ensure that the contract acceptor is fully
aware of any problems associated with the product or the work which
might pose a hazard to the environment, premises, equipment, personnel,
and other materials or products of the contract acceptor.
Article 282: The contract giver should supervise the entire process of
contract manufacturing or analysis.
Article 283: The contract giver should ensure that all of the materials
and products comply with corresponding specifications.
Section 3 The Contract Acceptor
Article284: The contract acceptor must have adequate premises and
equipment, knowledge and experience, and competent personnel to carry
out satisfactorily the manufacture or analysis work ordered by the
Article285: The contract acceptor should ensure that all materials,
intermediate and bulk products delivered by the contract giver are
suitable for their intended use.
Article 286: The contract acceptor should refrain from any activity
which may adversely affect the quality of the product manufactured
and/or analyzed for the contract giver.
Section 4 The Contract
Article287: A contract should be drawn up between the contract giver and
the contract acceptor which specifies their respective responsibilities
relating to the manufacture and control of the product. Technical
aspects of the contract should be drawn up by competent persons with
suitable knowledge in the pharmaceutical technology, analysis and the
provisions. All arrangements for manufacture and analysis must be in
accordance with the drug registration requirements and agreed by both
Article288: The contract should specify the way in which the qualified
person approving to release the batch for sale ensures that each batch
has been manufactured and checked for compliance with the requirements
of the Marketing Authorization.
Article 289: The contract should describe clearly who is responsible for
purchasing materials, testing and releasing materials, undertaking
production and quality controls (including in-process controls), and who
has responsibility for sampling and analysis. In the case of contract
analysis, the contract should state whether or not the contract acceptor
should take samples at the premises of the contract giver.
Article 290: The contract should define that processing, testing and
distribution records and samples kept by the contract acceptor, should
be available to the contract giver whenever needed. Any records relevant
to assessing the quality of a product in the event of complaints, a
suspected defect or recalls must be accessible to the contract giver.
Article 291: The contract should clearly define that the contract giver
can conduct on-site inspection or audit to the contract acceptor.
Article 292: The contract should define that the contract acceptor has
the obligation to accept the inspection conducted by drug regulatory
Chapter 12 Product Distribution and Recalls
Section 1 Principle
Article 293: The manufacturer should establish a recall system, if
necessary, to recall promptly and effectively any batch of products with
potential safety risks from the market.
Article294: Products returned and recalled due to quality problems
should be destroyed under supervision according to requirements, except
for those proved by evidences that the quality has not been compromised.
Section 2 Distribution
Article 295: Each batch of product should have a distribution record.
Based on the record, the sale of each batch should be traceable, when
necessary, all the products should be able to be taken back timely, The
distribution record should include information such as the product name,
strength, batch number, quantity, customer name, address, and contact
details, date of shipment, mode of transport, etc.
Article 296: Only two batches of remnant products are allowed in one
shared package. The two batch numbers shall be indicated on the outside
of the package, and a record for the shared packaging should be made.
Article 297: The distribution records should be retained for at least
one year after the shelf life of the finished product.
Section 3 Recalls
Article 298: Operation procedures for recall should be established to
ensure the effectiveness of recalls.
Article 299: A person should be designated as responsible for execution
and coordination of recalls and should be supported by sufficient staff.
This responsible person should be independent of the sales and marketing
organization. If this person is not the Authorized Person, the latter
should be made aware of any recall activity.
Article 300: Recall operations should be capable of being initiated at
any time and carried out promptly.
Article 301: Where a decision is made to recall a product from the
market due to its existing or potential safety risks, it should be
reported immediately to the drug regulatory department.
Article 302: The distribution records should be readily available to the
person(s) responsible for recalls.
Article303: Recalled products should be identified and stored separately
in a secure area awaiting a decision on their fate.
Article304: The progress of the recall process should be recorded, and a
final report should be issued, including the distributed and recalled
quantities of the products, along with the reconciliation between them.
Article305: The effectiveness of the product recall system should be
Chapter 13 Self Inspections
Section 1 Principle
Article 306: Self inspections should be organized periodically by the
quality management department to monitor the implementation of the
Provisions, evaluate whether the manufacturer is in compliance with
them, and to propose necessary corrective and preventive actions.
Section 2 Self Inspections
Article 307: A plan should be available for self inspections, and
periodical inspections should be conducted on organization and
personnel, premises, facilities, equipment, materials and products,
qualification and validation, documentation management, production
management, quality control and quality assurance, contract manufacture
and analysis, product distribution and recalls, and etc.
Article 308: Self inspections should be conducted in an independent,
systematic, and all inclusive way by the designated person(s) of the
manufacturer. Independent quality audits by external experts are also
Article 309: All self inspections should be recorded. Reports should be
prepared at the completion of self-inspections, and all the observations
made during the inspections, conclusions of evaluation, and proposals
for corrective and preventative actions should at least be included.
Self inspection status should be reported to the senior management of
Chapter 14 Supplementary Provisions
Article 310: The Provisions are basic requirements for
manufacturing and quality management of drugs. Special requirements for
sterile products, biological products and blood products, etc., or the
manufacturing and quality management activities, shall be separately
enacted as annexes by the State Food and Drug Administration.
Article 311: Manufacturers may use validated alternative approaches to
meet the requirements of the Provisions.
Article 312: Glossary:
1. Packaging: All operations, including filling and labeling, which a
bulk product has to undergo in order to become a finished product.
Aseptic filling, filling of products for terminal sterilization, and
etc., are not regarded as packaging.
2. Packaging materials: Any materials employed in the packaging of a
drug, including immediate packaging materials, container in direct
contact with drugs, and printed packaging materials, but excluding any
outer packaging materials used for transportation or shipment.
3. Operation Procedures: Approved documents to guide operations related
to the manufacture of drugs, such as equipment operation, maintenance
and cleaning, validation, environmental control, sampling, testing, and
etc. Also refer to as standard operating procedure (SOP).
4. Product: Includes the intermediate, bulk and finished product of
5. Product Lifecycle: All stages of the product from its development,
launch to market, till discontinuation.
6. Finished Product: A product which has undergone all stages of
production, including packaging in its final container.
7. Reworking: Subjecting all or part of a batch of intermediate or bulk
product which fails to meet the specifications to an alternate
manufacturing process in order to meet the predetermined specifications.
8. Bulk Product: Any product which has completed all processing stages
up to, but not including, final packaging.
9. Quarantine: The status of starting or packaging materials,
intermediate, bulk or finished products isolated physically or by other
effective means whilst storing and awaiting a decision on their release
or refusal before dispensing or marketing.
10. Dispense: A series of operations to circulate materials,
intermediate products, bulk products, documents, production molds, etc.
within the manufacturer.
11. Retest date: The date when a starting or packaging material, after
storage for a certain period, should be re-examined to ensure that it is
still suitable for its intended use. The retest date is determined by
12. Distribution: A series of operations to send the product from
manufacturer to the distributor or customer, including loading,
transportation, and etc.
13. Reprocessing: Subjecting all or part of a batch of intermediate,
bulk or finished products that fails to meet the specifications to a
previous step of the same manufacturing process in order to meet the
14. Release: The operation to make decisions, such as approval to use,
distribution into the market, or others, by evaluating the quality of a
batch of material or product.
15. Senior Management: Personnel on the top level of the manufacturer to
command and control it, and have the power and responsibility to
16. Master manufacturing documents: A document or set of documents
established with the purpose to produce a specified quantity of a
finished product, which include the manufacturing formula, processing
and packaging instructions, and specify the quantities of starting and
packaging materials, process parameters and conditions, a processing
description (including in-process controls), and precautions, etc.
17. Supplier: A party providing materials, equipment, instruments,
reagents or services, such as manufacturer, distributor, etc.
18. Recovery: The introduction of all or part of previous batches of the
required quality into another batch of the same product at a defined
stage of manufacture.
19. Computerized system: A system including the input of data,
electronic processing and the output of information to be used either
for reporting or automatic control.
20. Cross-contamination: Contamination of raw materials and excipients
(starting materials) or of a product with another material or product.
21. Calibration: The set of operations which establish, under specified
conditions, the relationship between values indicated by a measuring,
recording or controlling instrument or system (especially weighing), or
values represented by a material measure, and the corresponding known
values of a reference standard.
22. Campaign production: A manner adopted in a non-dedicated production
area to exclusively produce a product in a given period of time, conduct
a thorough cleaning of the production area, facilities, equipment,
tools, utensils, and etc. and then switch to another product.
23. Clean area: A room (or an area) with defined environmental control
of particulate and microbial contamination, constructed, outfitted and
used in such a way as to reduce the introduction, generation and
retention of contaminants within the room or area.
24. Alert limit: Established criteria giving early warning of drift of
the critical variables of a system from normal conditions, while not
reaching the action limit, which are not necessarily grounds for
definitive corrective action.
25. Action limit: Established criteria indicating that the critical
variables of a system are out of acceptable range, and requiring
investigation and corrective action.
26. Out of specification: All events that the testing results fail to
meet the regulatory standards or acceptance criteria established by the
27. Batch (or lot): A defined quantity of starting material, packaging
material or finished product processed in one process or series of
processes so that it could be expected as homogeneous. To complete
certain stages of manufacture, it may be necessary to divide a batch
into a number of subbatches, which are later brought together to form a
final homogeneous batch. In the case of continuous manufacture, the
batch must correspond to a defined fraction of the production,
characterized by its intended homogeneity. The batch size can be defined
either as a fixed quantity or as the amount produced in a fixed time
For example, the homogeneous product that solid or semi-solid
preparations for oral or topical use are produced within the same
blender by one blending prior to molding or filling should be regarded
as one batch. The homogeneous product that liquid preparations for oral
or topical use are produced by final mixing prior to filling (sealing)
should be regarded as one batch.
28. Batch number (or lot number): A distinctive combination of numbers
and/or letters which specifically identifies a batch.
29. Batch record: All relevant documents and records for the disposition
of a batch and includes processing, quality analysis and release review
information. Such documentation can be used to trace all history and
information related to the quality of finished product.
30. Air lock: An enclosed space with two or more doors, and which is
interposed between two or more rooms (e.g. of differing class of
cleanliness), for the purpose of controlling the air-flow between those
rooms when people or materials need to enter or exit. An air-lock is
designed for and used by either people or materials.
31. Manufacturer: Referred to as manufacturer of drugs, unless specified
otherwise in the Provisions.
32. Qualification: A series of actions proving that the premises,
facilities and equipment work correctly and actually lead to the
33. Return: Actions of sending back drugs to the manufacturer.
34. Documentation: The documentation in the Provisions includes
specifications, master manufacturing documents, operation procedures,
records, reports, and etc.
35. Materials: Raw materials and excipients packaging materials, and
For example, the raw materials for chemical drug preparations are
referred to as active pharmaceutical ingredients (APIs); those for
biological products are referred to as raw ingredients; those for
traditional Chinese medicine preparations are referred to as Chinese
crude drugs, prepared slices of Chinese crude drugs and outsourced
traditional Chinese medicine extracts; and the raw materials for the
APIs are referred to any substances used in the manufacture of APIs
excluding packaging materials.
36. Reconciliation: A comparison, making due allowance for normal
variation, between the amount of product or materials theoretically
produced or used, and actually produced or used plus loss collected.
37. Contamination: Adverse impacts of impurities with chemical or
microbiological properties or foreign matters, into starting materials,
intermediate, bulk, or finished products during production, sampling,
packaging or repackaging, storage or transport.
38. Validation: A series of actions of proving that any operation
procedure (or method), manufacturing process or system actually leads to
the expected results.
39. Printed packaging materials: Any packaging materials with specified
patterns and printed content, such as printed aluminum foil, labels,
insert sheets, and card boxes, and etc.
40. Staring materials: Any substance used in the production of a drug,
but excluding packaging materials.
41. Intermediate product: Partly processed product which must undergo
further manufacturing steps before it becomes a bulk product.
42. In-process control: Checks performed during production in order to
monitor and if necessary to adjust the process to ensure that the
product conforms to its specification. The control of the environment or
equipment may also be regarded as a part of in-process control.
Article 313: The Provisions shall be effective from March 1st, 2011.
According to Article 9 of the Drug Administration Law of the People’s
Republic of China, the specific implementation details and steps shall
be formulated by State Food and Drug Administration.