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The Regulations for Buildings and Facilities for Pharmacies etc. shall be revised as follows, in accordance
with the provisions of Article 6, Item 1 (including cases where it shall apply mutatis mutandis under
Article 26, Paragraph 2); Article 13, Paragraph 2, Item 1 (including cases where it shall apply mutatis
mutandis under Article 23); Article 28, Paragraph 3, Item 1; and Article 39, Paragraph 2 of the
Pharmaceutical Affairs Law (Law No. 145, 1960)
TABLE OF CONTENTS
Supplementary Provisions
DRUMBEAT
Concept
(Buildings and Facilities of Manufacturing Sites for Drugs to Which Standards for
Manufacturing Control and Quality Control Shall Not Apply)
Article 5 The buildings and facilities of manufacturing sites for drugs (excluding drugs
specified by the government ordinance pursuant to Article 13, Paragraph 2, Item 2 of the
Law, including cases where it shall apply mutatis mutandis under Article 18, Paragraph 2
of the law; the same in the next article, Article 5-3, and Articles 14 to 14-3 inclusive)
shall meet the following requirements.
(1) To have adequate facilities and equipment for manufacturing drugs at the 9.01
manufacturing site [including a material manufactured in the intermediate 10.01
process which must undergo further processes before a final product
(hereinafter referred to as “intermediate product”); excluding the
provisions of Article 10, Item 2; the same hereinafter].
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DRUMBEAT
Concept
A. To be adequately lighted, illuminated, ventilated and clean. 9.03.01
9.04
D. To have facilities for the control of dust, insects, and rodents. 1.09
9.03.01
9.05.02
9.07.02
(3) Among the work areas, work rooms for the weighing operations of raw
materials, and the formulating, filling or sealing operations of drugs
(including work rooms for active pharmaceutical ingredients where the
filling to sealing operations of intermediate products in containers after
the final purification are performed) shall meet the following operations.
C. To have entrances, exits and windows of the room that can be 11.01
locked. 12.02.09
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DRUMBEAT
Concept
E. To have floors made of concrete, tile, mortar or wood with a 9.07
smooth surface free from crevices, or of cleanable materials
equivalent thereto.
(4) To have adequate facilities for the sanitary and safe storage of raw 7.01
materials, packaging and labeling materials, and products.
(5) To have adequate facilities and equipment for the inspection and testing of 9.02.08
raw materials, packaging and labeling materials, and products. Proviso: 9.12
This provision shall not apply so long as the inspection and testing of
drugs undergoing only repackaging are performed on the manufacturer’s
own responsibilities using other testing institutions and this is confirmed
to present no problem and to be unavoidable.
(Buildings and Facilities of Manufacturing Sites for Drugs Other Than Active
Pharmaceutical Ingredients to Which the Standards for Manufacturing Control
and Quality Control of Drugs Shall Not Apply)
Article 5-2 The buildings and facilities of manufacturing sites for drugs other than active
pharmaceutical ingredients (limited to drugs specified by the government ordinance
pursuant to Article 13, Paragraph 2, Item 2 of the Law) shall meet the following
requirements.
(1) To have adequate facilities and equipment for manufacturing drugs at the 9.01
manufacturing site. 10.01
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DRUMBEAT
Concept
D. To have facilities for the control of dust, insects and rodents. 1.09
9.03.01
9.05.02
H. Among the work areas, the work room shall be provided with 9.03.01
structures and facilities for prevention of contamination by dust or
microorganisms according to the type, dosage form and
manufacturing process of intended drugs. Proviso: This provision
shall not apply so long as the same effects are obtained from the
functions of the manufacturing facilities.
K. Among the work areas, the work room for the weighing operations
of raw materials, and the formulating, filling or sealing operations
of drugs shall meet the following requirements.
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DRUMBEAT
Concept
(iii) To have no entrances or exits opening to the exterior, 9.01
except for emergency exits, shall be provided. 11.01
12.02.09
(iv) To have entrances, exits and windows of the room that can 11.01
be locked. 12.02.09
(4) To have adequate facilities for the sanitary and safe storage of raw 7.01
materials, packaging and labeling materials and drug products that are
separated.
(5) To have facilities for supply of water of the amount and quality required 5.19
for manufacture (including water for cleaning facilities and equipment as 9.08
well as containers; the same in the next article) according to the type of 9.08.01
drugs.
(6) To have facilities and equipment for the inspection and testing of raw 9.02.08
materials, packaging and labeling materials, and products. Proviso: This 9.12
provision shall not apply to the facilities and equipment for the following
inspection and testing so long as the inspection and testing are performed
on the manufacturer’s own responsibilities using the following testing
facilities or institutions and this is confirmed to present no problem and to
be unavoidable.
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DRUMBEAT
Concept
(Buildings and Facilities of Manufacturing Sites for Active Pharmaceutical
Ingredients to Which the Standards for Manufacturing Control and Quality
Control Shall Not Apply)
Article 5-3 The buildings and facilities of manufacturing sites for active pharmaceutical
ingredients (limited to drugs specified by the government ordinance pursuant to Article
13, Paragraph 2, Item 2 of the Law) shall meet the following requirements.
(1) To have adequate facilities and equipment for manufacturing drugs at the 9.01
manufacturing site.
(3) To have washing and toilet facilities and dressing rooms. 9.06
(4) Work areas shall meet the following requirements: Proviso: This provision
shall not apply to the requirements D and F when the manufacturing
process is carried out prior to the final purification, and manufacturing
facilities for such process have an enclosed structure.
D. To have facilities for the control of dust, insects and rodents. 1.09
9.03.01
9.05.02
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DRUMBEAT
Concept
H. Manufacturing facilities for active pharmaceutical ingredients 5.28
where substances causing anaphylaxis in minute or those 5.28.01
suspected to have serious effects on other drugs by cross- 6.18
contamination are produced in the intermediate process. When a
drug which is easily dispersed and causes anaphylaxis in minute
amounts shall have the functions to prevent other drugs from
contamination of such substances.
(5) The work area for performing manufacturing processes subsequent to the
final purification shall meet the following requirements in addition to
those in A to H of the preceding item.
A. Among the work areas, work rooms shall be provided with 9.03.01
structures and facilities for prevention of contamination by dust or
microorganisms according to the type, dosage form, physical
properties and manufacturing process of intended drugs. Proviso:
This provision shall not apply so long as the same effects are
obtained from the functions of the manufacturing facilities, etc.
C. Among the work areas, the work room for the filling to sealing
operations of intermediate products in containers which have
undergone the final purification shall meet the following
requirements.
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DRUMBEAT
Concept
(iv) To have entrances, exits and windows of the room that can 11.01
be locked. 12.02.09
(6) To have facilities for the sanitary and safe storage of raw materials, 7.01
packaging and labeling materials and products which are separated.
(7) To have facilities for supply of water of the quality and quantity needed 5.19
for manufacturing according to the type of drugs. 9.08
9.08.01
(8) To have facilities and equipment for the inspection and testing of raw 9.02.08
materials, packaging and labeling materials and products. Proviso: This 9.12
provision shall not apply to the facilities and equipment for the inspection
and testing of the following matters so long as the inspection and testing
are performed on the manufacturer’s own responsibilities using the
following testing facilities or institutions A to D and this is confirmed to
present no problem and to be unavoidable.
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DRUMBEAT
Concept
(Buildings and Facilities of Manufacturing Sites for Sterile Products)
Article 6 The buildings and facilities of the manufacturing sites for sterile products
[(injectable drug products, excluding blood products not constituting a lot pursuant to
Article 1, Paragraph 2 of the Regulations for Manufacturing Control and Quality Control
of Drugs and Quasi-drugs (MHW Ministerial Ordinance No. 16, 1999), eye drops, eye
ointment or biological products (excluding blood products not constituting a lot, and
drugs intended for exclusive use in the diagnosis of diseases and those directly used in
the human body; the same in this article and Article 7), and water for injections; the same
hereinafter) shall meet the following requirements in addition to those specified under
Article 5-2.
A. Among the work areas, the work room or working control area 1.12
(the area consisting of work rooms, passage, etc. that are 9.03
controlled so as to maintain a uniform quality of cleanliness; the 9.03.01
same hereinafter) shall be provided with adequate structures and
facilities for maintaining appropriate temperature, humidity and
cleanliness according to the type, dosage form and manufacturing
process of intended sterile products.
B. The work room for the weighing operations of raw materials and 9.03.02
for the washing operations of containers shall have an enclosed
structure for protection against dust.
C. The work room for the drying and sterilization operations of 1.12.03
containers after washing shall be used exclusively for that purpose. 9.02.10
Proviso: This provision shall not apply so long as there is no risk
of contamination of containers after washing.
D. The work room or work control area for the formulating, filling or
sealing operations of drugs shall meet the following requirements.
(i) To be separated from the work area for drugs other than 9.02
sterile products and sterile active pharmaceutical
ingredients (refer to active pharmaceutical ingredients that
are sterile, excluding intermediate product; the same
hereinafter). Proviso: This provision shall not apply so long
as there is no risk of contamination of sterile products.
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DRUMBEAT
Concept
(ii) The ceilings, walls and floors of the room shall have 9.07
surfaces made of materials able to withstand spray washing
with disinfectant solutions.
(iv) The work room for the formulating operations and for the 1.12
filling or sealing operations shall be used exclusively for 9.02
their respective purposes. Proviso: When the formulating
and filling operations, or the formulating, filling or sealing
operations are performed continuously in a closed system,
these operations may be performed in the same room.
When the filling and sealing operations of sterile products
other than injections are performed in a closed system, both
operations may be performed in the same room as the
formulating operations. Separate rooms for the preparing
operations and for the filling or sealing operations of
radiopharmaceuticals shall not be used.
(v) When injectable drug products and other sterile products 1.12
are manufactured in the same room, manufacturing 9.02
facilities for injectable drug products shall be in a closed
system and used exclusively for that purpose.
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DRUMBEAT
Concept
E. In the case of liquid injectable drug products, purification 5.30.01
equipment for air replenished in a tank for storing stock solutions.
(3) To have sterilization equipment for manufacturing according to the type 10.01
of intended sterile products.
(4) To have indoor facilities for manufacturing distilled water, etc. (including 5.19
cleaning water for facilities and equipment, and containers; the same
hereinafter) of the quality or quantity needed for manufacturing according
to the type of sterile products. Proviso: It is not necessary to install these
facilities indoors when they have an enclosed system.
(5) Facilities such as pipes to supply distilled water, etc. for manufacturing 5.19.01
shall be constructed so as to prevent contamination of distilled water, etc. 5.19.02
by foreign matter or microorganisms.
(6) The following facilities and equipment for the inspection and testing of 9.02.08
the following matters shall be provided. In such cases, the proviso in Item 9.12
6, Article 5-2 shall apply mutatis mutandis.
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DRUMBEAT
Concept
(Buildings and Facilities of Manufacturing Sites for Sterile Active Pharmaceutical
Ingredients)
Article 6-2 The buildings and facilities of manufacturing sites for sterile active
pharmaceutical ingredients shall meet the following requirements in addition to those
specified under Article 5-3.
A. Among the work areas, the work room or working control area 1.12
shall be provided with adequate structures and facilities for 9.03
maintaining appropriate temperature, humidity and cleanliness 9.03.01
according to the type, physical properties and manufacturing
process of intended sterile active pharmaceutical ingredients.
B. The work room for washing containers (limited to those used in 1.12.03
the operations subsequent to the preparing operations intended for 9.02.10
sterilization; the same in this article) shall have an enclosed
structure for protection against dust.
(i) To be separated from the work area for drugs other than 9.02
sterile products and sterile active pharmaceutical
ingredients. Proviso: This provision shall not apply so long
as there is no risk of contamination of sterile active
pharmaceutical ingredients.
(ii) The ceilings, walls and floors of the room shall have their 9.07
surfaces made of materials able to withstand spray washing
with disinfectant solutions.
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DRUMBEAT
Concept
E. To have dressing rooms for exclusive use by personnel engaged in 9.06
operations in specified in D.
(2) The work area shall be provided with the following facilities and
equipment.
(3) To have sterilization facilities for manufacturing according to the type of 9.02
sterile active pharmaceutical ingredients. 9.15
(4) To have indoor facilities for manufacturing distilled water, etc. of the 5.19
quality and quantity needed for manufacturing according to the type of
sterile active pharmaceutical ingredients. Proviso: It is not necessary to
install these facilities indoors when they have an enclosed structure.
(5) Facilities such as pipes to supply distilled water, etc. required for 5.19.01
manufacturing shall be constructed so as to prevent contamination of 5.19.02
distilled water, etc. by foreign matter or microorganisms.
(6) To have the following facilities and equipment for inspection and testing. 9.02.08
In such cases, the proviso of Article 5-3, Item 8 shall apply mutatis 9.12
mutandis.
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DRUMBEAT
Concept
D. Facilities and equipment for sterility tests
(1) The work area for biological preparations shall be provided with the
following facilities. Proviso: The facilities confirmed it unnecessary to
manufacture the preparations according to the type, manufacturing
method, etc. of biological preparations shall be excluded.
H. Facilities for diluting and subdividing stock solutions and for 9.02.15
sealing containers.
I. Facilities for disinfecting devices and equipment that have been 1.04
used in manufacturing or in testing
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DRUMBEAT
Concept
(2) The facilities specified under the preceding item shall be provided with 5.28.01
rooms which are distinctly separated from other rooms, and rooms 6.18
provided with the facilities indicated in A, B, D or I of the preceding item,
which are used to treat smallpox viruses, acute poliomyelitis viruses,
spore-forming pathogens or Mycobacterium tuberculosis, shall be used
exclusively for treating each type of biological preparation and strictly
isolated from other rooms.
(3) The ceilings, walls and floors of the room provided with the facilities 9.07
indicated Item 1, B to D, and F to H shall have their surfaces constructed
so as to allow washing and disinfection.
(4) The room provided with the facilities indicated in Item 1, D and F to H
inclusive and the room provided with the facilities for the sterility tests,
among the facilities for testing raw materials, labeling and packaging
materials, shall meet the following requirements.
A. Work rooms shall be aseptic. Proviso: This provision shall not 1.12
apply so long as a room provided with an aseptic box where 1.12.01
aseptic operations can be carried out, according to the type,
manufacturing method, etc. of biological preparation.
(5) The work area shall be provided with the following facilities in addition to
those specified in Item 1.
B. Facilities for preparing culture media and diluents for the media.
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DRUMBEAT
Concept
(6) Storage facilities shall be provided with thermostats, self-recording 7.01
thermometers and other required meters. 10.04
(i) The ceilings, walls and floors with a smooth surface and 9.07
free from crevices shall be constructed so as to prevent dust 9.07.02
and dirt from falling.
B. The outlet for discharge shall not be provided with the clean area.
Proviso: This provision shall not apply so long as the requirements
in the following (i) to (iii) are met and this is confirmed to present
no problem.
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DRUMBEAT
Concept
(i) The outlet for discharge shall be provided with drainage 5.19
trap that is easy to clean, and equipment for preventing 9.07.01
water from flowing backward. 9.08.02
(ii) The trap shall have structures that can be disinfected. 9.07.01
9.08.02
(iii) The grooves of the floor shall be shallow, easy to clean and 9.07
connect through the outlet for discharge to the outside of 9.07.01
the manufacturing area (refer to a site for performing the
operations to incubate, extract and purify, weigh raw
materials, wash and dry containers, formulate and fill
drugs, and to seal and package containers, as well as a site
for dressing; the same in this item).
(i) The outlet for discharge shall not be provided with the 1.12
aseptic area.
(ii) The sink shall not be provided with the aseptic area. 1.12
D. The area for performing tests using animals and microorganisms, 9.02.08
and for treating animal tissues and microorganisms that are not 9.02.15
used in manufacturing biological preparations etc. shall be
distinctly separated from other areas for manufacturing biological
preparations etc., and air handling systems shall be exclusively
provided.
E. The area for performing aseptic operations shall be provided with 9.03.01
structures and facilities for controlling positive pressure.
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DRUMBEAT
Concept
H. The area for manufacturing drugs with human blood or plasma as 9.02
raw materials shall be distinctly separated from other areas and
shall be provided with facilities and equipment exclusively for
manufacturing such drugs. Proviso: This provision shall not apply
to the area for performing the processes subsequent to the virus
inactivation or elimination.
(3) Pipes, valves and bent filters shall be constructed so as to facilitate 10.01
cleaning and sterilization according to the purpose of use.
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DRUMBEAT
Concept
(4) Facilities for keeping animals for use in manufacturing or in testing 9.11
(including donor animals; hereinafter, refer to as “use animals” in this
item) shall meet the following requirements.
A. To have quarantine areas for use animals are separated from other
areas.
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DRUMBEAT
Concept
(Buildings and Facilities of Manufacturing Sites for Quasi-drugs to Which
Standards for Manufacturing Control and Quality Control Shall Not Apply)
Article 12 To the buildings and facilities of manufacturing sites for quasi-drugs 9.01
(excluding quasi-drugs stipulated by the government ordinance pursuant to Article 13, 10.01
Paragraph 2, Item 2 of the Law), the provisions of Article 5 (excluding Item 5) shall
apply mutatis mutandis, and adequate facilities and equipment for the inspection and
testing of raw materials, labeling and packaging materials, and products shall be
provided. Proviso: This provision shall not apply to the facilities and equipment for the
inspection and testing of the following matters so long as the inspection and testing are
performed on the manufacturer’s own responsibilities using the following testing
facilities or institutions and this is confirmed to present no problem to the proper testing.
(2) High level physicochemical or animal tests: other testing facilities for the
manufacturer or testing institutions specified under Article 11, Paragraph
1 of the Enforcement Regulations.
(1) To be provided with adequate facilities and equipment for manufacturing 9.01
of products at the manufacturing site. 10.01
(2) To have work areas which shall meet the following requirements.
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DRUMBEAT
Concept
D. To be provided with facilities for the control of dust, insects and 1.09
rodents. 9.03.01
9.05.02
(3) To be provided with adequate facilities for the sanitary and safe storage of 7.01
raw materials, labeling and packaging materials, and products.
(4) To be provided with adequate facilities and equipment for the inspection 9.02.08
and testing of raw materials, labeling and packaging materials, and 9.12
products. Proviso: This provision shall not apply to the facilities and
equipment for the inspection and testing of the following matters so long
as the inspection and testing are performed on the manufacturer’s own
responsibilities using the following testing facilities or institutions and this
is confirmed to present no problem to the proper testing.
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Supplementary Provisions
DRUMBEAT
Concept
(Date of Enforcement)
1. This ordinance shall come into effect on the date of enforcement (February 1,
1961).
Attached Table
Sign Size Location of Sign
On radioactivity signs as specified Radioactivity signs shall have a The sign shall be posted at the
under Article 17, Paragraph 1 of radius of at least 10 cm. entrance or exit of the storage
the Japan Industrial Standards in room or its vicinities.
accordance with the Industrial
Standardization Law (Law No.
185, 1949), the upper part shall
indicate “Storage Room” and the
lower part “Unauthorized Entry
Prohibited.”
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II. Regulations for Manufacturing Control and Quality Control of Drugs and Quasi-drugs
In accordance with the provisions of Article 13, Paragraph 2, Item 2 (including cases where it shall apply
mutatis mutandis under Article 18, Paragraph 2) of the Pharmaceutical Affairs Law (Law No. 145, 1960),
the whole text of the Regulations for Manufacturing Control and Quality Control of Drugs and Quasi-
drugs shall be revised as stated below.
TABLE OF CONTENTS
Supplementary Provisions
DRUMBEAT
Concept
(Definitions)
Article 1 The term “labeling and packaging materials” used in this ordinance means
containers, wrappers and package inserts of a product, and labels pasted on the containers
and wrappers.
2. The term “lot” used in this ordinance means a batch of products manufactured so
as to have a uniform quality during a series of manufacturing processes within a
unit of manufacturing period [including a material manufactured during the
process which must undergo subsequent processes before a final product is
obtained (hereinafter referred to as “intermediate product”; the same under
Article 3, Paragraph 1, Item 2; Article 6, Paragraph 1, Item 2-D and Paragraph 2,
Item 1-A, G and J; and Article 8, Paragraph 1, Item 1-A and B) and raw
materials.
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DRUMBEAT
Concept
3. The term “control unit’ used in this ordinance means a batch of labeling and
packaging materials which are confirmed to have a uniformity quality.
4. The “validation” used in this ordinance means to validate and document that
anticipated results yield from the buildings and facilities at manufacturing sites as
well as operating procedures, processes and other methods of manufacturing
control and quality control (hereinafter referred to as “the operating procedures
etc”).
5. The term “clean area” used in this ordinance means, among the areas for
performing manufacturing operations (hereinafter referred to as “work area”), a
place for performing the weighing operations of raw materials and the preparing
operations of drugs, and a place where containers after washing are exposed to
the air in the work area.
6. The term “aseptic area” used in this ordinance means, among the work area, a
place where drugs being sterile and containers after sterilization are exposed to
the air in the work area, a place for performing the filling operations of drugs and
the sealing operations of containers, as well as a place for performing aseptic
operations such as sterility tests etc.
7. The term “cellular/tissue based drug” used in this ordinance means drugs
composed of human or animal cells or tissues (excluding human blood and drugs
composed of ingredients manufactured with human blood).
8. The term “donor” used this ordinance means an individual providing her (his)
cells or tissues as raw materials of cellular/tissue based drugs (excluding cells or
tissues derived from the human body with brain death as specified under Article
6, Paragraph 2 of the Law on Organ Transplantation (Law No. 104, 1997).
9. The term “donor animal” used in this ordinance means an animal providing its
cells or tissues as the source materials of cellular/tissue based drugs.
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DRUMBEAT
Concept
Section 1 General Rules
(Manufacturing Control Manager and Quality Control Manager)
Article 2 A manufacturer of drugs (hereinafter referred to as “manufacturer”) shall 13.01
designate, at each manufacturing site, a person responsible for the manufacturing control 13.02
unit as the manufacturing control manager and a person responsible for the quality 13.11
control unit as the quality control manager, who perform their duties under the
supervision of a product security pharmacist (hereinafter referred to as “product security
pharmacist”).
2. The quality control unit shall be independent of the manufacturing control unit.
3. The manufacturing control manager shall not hold a position as the quality
control manager concurrently.
(1) To supervise the manufacturing control manager and the quality control
manager.
(3) To ensure that the validation, self-inspection and training, as well as the
confirmation specified under Article 15, Paragraph 5, Item 1, are properly
carried out, by documents reported as specified under Article 10,
Paragraph 1, Item 2; Article 13, Paragraph 1, Item 2; Article 14,
Paragraph 1, Item 2; and Article 15, Paragraph 5, Item 2.
2. The manufacturer shall make efforts for the effective performance of the duties
assigned to the product security pharmacist.
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DRUMBEAT
Concept
(1) Terms concerning manufacturing approval;
(3) In cases where drugs intended for manufacture are biological products
specified under Article 2, Paragraph 5 of the Law (Law No. 145, 1960)
(hereinafter referred to as “biological product”), biological preparations
indicated in Item 2-A, Paragraph 2, Article 15-4 of the Enforcement
Ordinance of the Law (Government Ordinance No. 11, 1961), drugs
designated by the Minister pursuant to the provisions of Article 43,
Paragraph 1 of the Law, drugs manufactured by application of gene
recombination technology, drugs provided as the source materials drugs
manufactured by application of gene recombination technology, drugs
manufactured by application of incubation technology of human or animal
cells, or drugs provided as the source materials drugs manufactured by
application of incubation technology of human or animal cells, or
cellular/tissue based drugs (hereinafter referred to as “biological
preparations etc.”), describe the following matters.
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DRUMBEAT
Concept
(Duties of Manufacturing Control Manager)
Article 6 The manufacturer shall have the manufacturing control manager perform 13.05
appropriately the following duties related to the manufacturing control of drugs in
accordance with the product master formula, the manufacturing control standard code or
the manufacturing hygiene control standard code.
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DRUMBEAT
Concept
(3) To confirm from records of storage, receipt/distribution, as well as those 8.01.01
of the manufacturing hygiene control that the manufacturing control is
properly performed, and report the results of the confirmation in writing to
the product security pharmacist.
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DRUMBEAT
Concept
A. When source materials or products are inactivated, or 5.28
microorganisms etc. contained in the source materials and products
are inactivated or eliminated, during the manufacturing process, to
take action necessary for preventing contamination by the source
materials or products that are inactivated or eliminated in such a
way.
E. To restrict as much as possible for personnel other than those who 12.02.09
are engaged in manufacturing to go in or out of the work area.
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DRUMBEAT
Concept
(i) To have personnel engaged in manufacturing wear work 1.12.02
clothes, shoes, caps and masks that have been disinfected. 12.02.05
12.02.06
(iii) When personnel having their conditions that are suspected 12.02.02
to contaminate raw materials or products with abnormal
numbers or types of microorganisms (including infectious
diseases such as skin or hair, cold, wound, or symptoms
such as diarrhea or fevers without causes), to have each
personnel notify the fact.
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DRUMBEAT
Concept
(iii) Biological properties and date of testing.
(i) A period of the expiry date plus 30 years for specified biological 8.01.01
products or for products containing human blood derived material.
(ii) A period of the expiry date plus 10 years for biological products 8.01.01
(excluding products indicated in (i)).
(i) A period of the expiry date plus 30 years for specified biological 8.01.01
products or for products containing human blood derived material.
(ii) A period of the expiry date plus 10 years for biological products 8.01.01
(excluding products indicated in (i)).
(2) To prepare records specified in Item 4 of the preceding paragraph and L 8.01
and M indicated in the preceding item from each lot of intended biological
products etc., and to retain the records thereof.
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3. In manufacturing cellular/tissue based drugs, the manufacturer shall, in addition
to the duties in Paragraph 2, have the manufacturing control manager perform
properly the following duties related to the manufacturing control of
cellular/tissue based drugs in accordance with the product master formula, the
manufacturing control standard code, or the manufacturing hygiene control
standard code.
(iii) When the cells or tissues are derived from humans, the
status of diagnosing donors through their health checking
and testing for the donor screening (refer to a decision of,
from the results of the health checking and testing of
donors, whether or not such donors are fully eligible to
provide their cells or tissues as source materials of
cellular/tissue based drugs.
(iv) When cells or tissues are derived from animals, the status
of receiving donor animals, as well as conditions of the
inspection and testing, and breeding and keeping of such
animals for the donor screening (refer to a decision of,
from the results of the health checking and testing of donor
animals, whether or not such donors are fully eligible to
provide their cells or tissues as source materials of
cellular/tissue based drugs).
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(vi) Requirements for ensuring the quality of cellular/tissue
based drugs, in addition to those indicated in (i) to (v)
above.
E. For products, to grasp, for each product, the name of the 7.02
destination facilities and date of distribution, and lots, and to
prepare the records thereof.
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4. Records of biological products specified in the preceding three paragraphs shall 8.01.01
be retained appropriately so as to confirm a series of records biologically derived
source materials provided in manufacturing to a product manufactured with the
biologically derived source materials.
A. To collect samples of raw materials and products by lot, and those 3.03
of labeling and packaging materials by control unit, and to prepare 6.01
the records thereof. 6.01.05
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(iii) High level physicochemical and animal tests of the
product: Other testing facilities of the manufacturer, or the
testing institutions specified under Article 11, Paragraph 1
of the Enforcement Regulations.
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D. To perform the periodical inspection for maintenance of the testing 2.02
facilities and equipment (including calibration of meters), and to 2.02.04
prepare the records of the inspection. 6.12
(2) To report evaluation of test results in writing to the product security 6.16
pharmacist and the manufacturing control manager.
(3) To retain records of test results for the following duration from the date of 8.01.01
preparation.
A. Three years for drugs other than biological products etc. [when the
drug related to the records is obliged to state the expiry date, a
period of the expiry date plus one year].
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D. To dispose of all the articles which have been contaminated with 1.19
microorganisms (limited to those contaminated during the
inspection and testing) and carcasses of use animals so as not to
cause hazards to the public health and hygiene.
(1) To perform by herself/himself the inspection and testing of donor animals 6.27
at the time of or after their receipt and other necessary duties, or to have a
person, designated beforehand, perform the following duties according to
the type of duties (when the drug related to the records is a specified
biological product or a product containing human blood derived materials,
a period of the expiry date plus 30 years).
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(2) To prepare records of the duties in the preceding item, and to retain the 8.01.01
records thereof for a period of the expiry date plus 10 years (when a drug
related to the records is a specified biological product or a product
containing human blood derived material, a period of the expiry date plus
30 years.
4. Records of biological products specified in the preceding three paragraphs shall 8.01
be retained appropriately so as to confirm a series of records from biologically
derived source materials provided in manufacturing to a product manufactured
with biologically derived source materials.
(Validation)
Article 10 The manufacturer shall have a person, designated beforehand, perform the
following duties in accordance with the operating procedures.
B. When there are changes made in the operating procedures, which 5.04.01
might have serious effects on the quality of drugs.
(2) To report in writing to the product security pharmacist the results of 17.04
validation.
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(3) To retain records of validation for the following periods from the date of 8.01.01
preparation.
2. The manufacturer shall take all the required action when it is found necessary to 8.01.01
improve the manufacturing control and quality control from the results of the
validation in Item 1 of the preceding paragraph, prepare records of the action
taken, and to retain the records thereof for the following periods from the date of
the preparation.
(1) Three years for drugs other than biological products etc.
(2) A period of the expiry date plus 30 years for specified biological products
or products containing human blood derived material.
(3) A period of the expiry date plus 10 years for biological products etc.
(excluding products indicated in the preceding item).
(Complaint Management)
Article 11 When there is a complaint regarding the quality etc. of drugs, the 6.13
manufacturer shall have the product security pharmacist perform the following duties in
accordance with the operating procedures, excluding cases where the complained matter
is not obviously attributable to the manufacturing site.
(1) To investigate into the cause of the complaint, and to take all the required 6.21.06
action when it is found necessary to improve the manufacturing control
and quality control.
(2) To prepare records of the complaint management describing the details of 6.13
the complaint, clarified cause, and the correction action taken, and to 8.01.01
retain the records thereof for the following periods from the date of
preparation.
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B. A period of the expiry date plus 30 years for specified biological
products or products containing human blood derived material.
(Recall Action)
Article 12 The manufacturer shall, when taking a recall action for the reason the quality 7.05
etc. of drugs, have the product security pharmacist of the manufacturing site perform the
following duties in accordance with the operating procedures, excluding cases where the
recall is not obviously attributable to the manufacturing site.
(1) To investigate into the cause of the recall, and to take all the required 6.21
action when it is found necessary to improve the manufacturing control
and quality control.
(2) To store by separation of the recalled products for a given period, and to 7.04.02
properly dispose of them.
(3) To prepare records of the recall action taken describing the details of the 7.05.01
recall, clarified cause, and the correction action taken, and to retain the 8.01.01
records thereof for the following periods from the date of preparation.
(Self-inspection)
Article 13 The manufacturer shall have a person, designated beforehand, perform the
following duties in accordance with the operating procedures.
(1) To perform the periodical self-inspection of the manufacturing control and 6.12
quality control of drugs at the manufacturing site.
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(3) To prepare records of the self-inspection results, and to retain the records 8.01.01
thereof for the following periods from the date of the preparation.
2. The manufacturer shall take all the required action when it is found necessary to 6.12
improve the manufacturing control and quality control from self-inspection 8.01.01
results in Item 1 of the preceding paragraph, and prepare records of the action
taken, and to retain the records thereof for the following periods from the date of
preparation.
(1) Three years for drugs other than biological products etc.
(2) A period of the expiry date plus 30 years for specified biological products
or products containing human blood derived material.
(3) A period of the expiry date plus 10 years for biological products etc.
(excluding products indicated in B).
(Training)
Article 14 The manufacturer shall have a person, designated beforehand, perform the
following duties in accordance with the operating procedures.
(2) To report the status of the training in writing to the product security 5.06.03
pharmacist.
(3) To prepare records of the training, and to retain the records thereof for 3 5.06.03
years from the date of preparation. 8.01.01
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(1) To conduct training of personnel engaging in the manufacturing or inspection and 5.06
testing of biological products etc. in microbiology, medicine, veterinary medicine,
etc.
(2) To conduct training of personnel working in the aseptic area or other areas where 1.12.02
pathogenic microorganisms are treat, for taking action to prevent contamination 5.06.05
by microorganisms.
(3) Periodical confirmation by the contractor of the proper conduct of the 14.01.03
contract manufacture at the manufacturing site of the contract acceptor.
(4) Instructions of the contractor given to the contract acceptor with respect to
the contract manufacture.
(5) When the contractor gives instructions specified in the preceding item that
any necessary action should be taken to improve the manufacturing
control or quality control of the contract manufacture, confirmation by the
contractor that such action has been taken.
(7) Other matters required to ensure the proper conduct of the manufacturing
control and quality control of the contract manufacture.
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2. The contractor and the contract acceptor shall document matters for the contract 14.01.02
specified in the preceding paragraph in the product master formula,
manufacturing control standard code, manufacturing hygiene control standard
code, quality control standard code, and operating procedures. Proviso: In such
cases, each of the contractor and the contract acceptor should document only the
processes performed by herself/himself, notwithstanding the provisions of Article
4, 5, 7, and 9.
3. The contractor shall give written instructions specified in Paragraph 1, Item 4. 14.01
4. The contract acceptor shall report in writing to the contractor that the security 14.01.02
pharmacist of the contract acceptor has released the products through appropriate
evaluation of the manufacturing control and quality control of the contract
manufacture.
5. The contractor shall have a person, designated beforehand, perform the following
duties.
(3) To prepare records after the date of expiration specified in Item 1, and to 8.01.01
retain the records thereof for the following periods after the date of
preparation.
Article 15-2 The contractor may provide instructions, instead of written instructions 14.01
specified in Paragraph 3 of the preceding article, by using an electronic system of
information processing or by the following methods utilizing information
communication technologies (hereinafter referred to as “electromagnetic methods” in this
article) after having obtained the consent of the contract acceptor as specified in
Paragraph 4. In such cases, it shall be recognized that the contractor has provided written
instructions.
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(1) The following method A or B among the methods of using an electronic 2.06.03
system of information processing shall be used.
(2) The method to distribute instructions entered in the files prepared with 2.06.03
means capable of providing a safe entry to given matters, including a
magnetic disk, CD-ROM or other equivalent means.
2. The methods specified in the preceding paragraph shall allow the contract
acceptor to prepare a document by output of data entered in the files.
(1) The method available to the contractor among the methods specified in
Paragraph 1.
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5. When the contractor obtaining the consent specified in the preceding paragraph is
informed in written or by the electromagnetic methods that the contract acceptor
refuses to obtain instructions by electromagnetic methods, the contractor shall not
give instructions specified in Paragraph 3 of the preceding article by
electromagnetic methods. Proviso: This provision shall not apply when the
contract acceptor has given the consent specified in the preceding paragraph.
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(Manufacturing Control and Quality Control of Quasi-drugs)
Article 17 The provisions in Chapter 2 (excluding Article 4, Item 3; Article 6, Paragraph
2; Article 8, Paragraph 2; and Article 14, Paragraph 2) shall apply to quasi-drugs. In this
case, “product security pharmacist (hereinafter referred to as “product security
pharmacist”) under Article 2, Paragraph 1 shall read “responsible engineering manager”,
and “product security pharmacist” in Chapter 2 (excluding Article 2, Paragraph 1) shall
read “responsible engineering manager”.
Supplementary Provisions
DRUMBEAT
Concept
(Date of Enforcement)
1. This ordinance shall come into effect on March 31, 1999.
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