INTRODUCTION
The fi rst predecessors of manufacturing and quality requirements, which later
evolved into good manufacturing practices (GMPs), were issued in the 1940s in the
United States by the Food and Drug Administration (FDA) [1] . In the general
meeting of the World Health Organization (WHO) held in 1969, the World Health
Assembly issued a recommendation for the introduction of GMPs [2] . Since then,
most industrialized countries have passed laws on control procedures essential for
the manufacture of drug products. In some countries GMPs are integrated into
national legislation as a part of laws or regulations on production, distribution,
marketing, and use of drug products (GMP regulations). In other countries, GMPs
are separate guidelines outside the national drug legislation (GMP codes). In addition
to national GMPs, also some international organizations and trade blocks have
issued their own international GMP guidelines to harmonize the requirements for
drug production in different countries. However, regardless of their origin, the main
purpose of GMPs is to ensure that manufactured drug products have the safety,
identity, potency, purity, and quality that they are presented to have [3] . To fulfi ll
this aim, most GMPs usually cover quality management, personnel, premises, equipment,
documentation, materials management, production and in - process controls,
packaging and labeling of intermediate and fi nished products, laboratory controls,
validation, and change controls
NATIONAL GMP REGULATIONS AND CODES
2.1.2.1 United States
In the United States the production of drug products is controlled under the federal
Food, Drug and Cosmetic Act, which states that a drug product will be deemed to
be adulterated unless the methods used in or the facilities or controls used for its
manufacture, processing, packaging, or holding conform to or are operated or
administered in conformity with current GMP [5] . The actual GMP regulations are
issued as a part of the Code of Federal Regulations and as such they are a federal
law. The current set of GMP regulations is based on the 1978 revision [6, 7] of the
original GMP regulations, which were fi rst promulgated in 1963. The GMP regulations
are updated every year in April [8] ; however, no major changes have been
implemented since 1978. As an addition to GMP regulations, the FDA also publishes
other GMP - related guidance documents covering various issues of drug manufacturing
[9] . On the other hand, although these documents refl ect current views andexpectations of the agency, they only provide guidance on principles and practices
that are not legal requirements [1] . As a member of the International Conference
on Harmonization of Technical Requirements for Registration of Pharmaceutical
for Human Use (ICH), the United States has adopted the ICH guidance document
Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, and
published it as a guidance for industry document [10] .
The U.S. GMP regulations are divided into two parts: 210 [6] and 211 [7] . Part
210, “ Current Good Manufacturing Practice in Manufacturing, Processing, Packing
or Holding of Drugs — General, ” provides the framework for the regulations [6] , and
Part 211, “ Current Good Manufacturing Practice for Finished Pharmaceuticals, ”
states the actual requirements. Part 211 is further divided into 11 subparts, which
cover the requirements for personnel, premises, equipment, control of materials,
production and process controls, packaging and labeling control, holding and distribution,
laboratory controls, documentation, and returned and salvaged products [7] .
The contents of Part 211 are presented in Table 1 .
2.1.2.2 Canada
The production of drug products (drugs) in Canada is controlled under the Food
and Drugs Act, which states that distributors and importers are not allowed to sell
a drug product unless it has been manufactured according to the requirements of
GMP. The principles of GMP are laid down by Division 2 in Part C of the Food and
Drug Regulations, which is a part of the Food and Drugs Act [11] . The Health
Products and Food Branch Inspectorate has also issued a guidance document (GMP
code), which has been prepared to assist in the interpretation of GMP regulations.
The current set of the Canadian GMP code was issued in 2002 and has not been
revised since. It has been written with a view to harmonization with GMP standards
of other countries and international organizations [WHO, Pharmaceutical Inspection
Cooperation Scheme (PIC/S), ICH]. Canadian Healthcare authorities have also
published several annexes to the basic GMP code covering topics such as GMP for
medical gases, biological drug products, blood products, and production of investigational
new drugs. In addition to the GMP code and its annexes, the Canadian2.1.2.4 East Asian Countries
Japan In Japan the production of drug products (drugs) is regulated under the
Pharmaceuticals Affairs Law (PAL), which states that any drug manufacturer who
plans to manufacture a drug product for sale in Japan must have a Japanese drug
manufacturing license and comply with Japanese GMP requirements. The fi rst regulations
of Japanese GMP were introduced in 1974 as The Standards for Manufacturing
Control and Quality Control . In 1979 PAL was partially revised and GMPs
became legally binding [2] .
PAL is managed and enforced via ministerial ordinances and notices, which are
detailed regulations prepared by the Japanese government. The requirements for
premises for drug manufacture are given in Ministry of Health, Labor and Welfare
(MHLW) Ministerial Ordinance No. 73, 2005 Regulations for Buildings and Facilities
for Pharmacies, etc. [originally Ministry of Health and Welfare (MHW) Ministerial
Ordinance No. 2, 1961] [17] , and the requirements for manufacturing and quality
controls in MHLW Ministerial Ordinance No. 95, 2003 Regulations for Manufacturing
Control and Quality Control of Drugs (originally MHW Ministerial Ordinance
No. 3, 1994). As a member of the ICH Japan has adopted the ICH guidance
document Q7, Good Manufacturing Practice Guide for Active Pharmaceutical
Ingredients , and published it as Pharmaceutical and Food Safety Bureau (PFSB)
Director - General Notifi cation No. 1200, 2001 Guidelines on GMP for Drug Substances
, which states the requirements for the manufacture of APIs. The requirements
concerning imported drug products are given in MHLW Ministerial Ordinance
No. 97, 2003 Regulations for Importing/Retail Management and Quality Control of
Drugs and Quasi - Drugs (originally MHW Ministerial Ordinance No. 62, 1999). The
requirements specifying manufacture of investigational products are given in PAB
Notifi cation No. 480, 1997 Products and Standards for the Buildings and Facilities of
Manufacturing Plants for Investigational Products (Investigational Product GMP)
[2] .
South Korea The production of drug products (drugs) in South Korea is regulated
under the Pharmaceutical Affairs Law, which was fi rst enacted in 1953 and has since
been revised several times [18] . New drug approval and related activities are regulated
in much the same way as in the United States and Japan. Korean GMP, which
is often called KGMP, was initiated in 1984 and became mandatory in 1995 [19] . A
drug manufacturer who intends to manufacture a drug product for sale in Korea
must have approval from the Commissioner of the Korea Food and Drug Administration
(KFDA). In order to require the license for manufacturing business the
manufacturer has to prove the compliance of facility standards with KGMP [20] .
China China regulates the production of drug products (drugs) under the Drug
Administration Law of the People ’ s Republic of China, which states that a drug
manufacturer has to conduct drug manufacture according to the GMP for pharmaceutical
products formulated by the Drug Regulatory Department under the State
Council on the basis of the Drug Administration Law [21] . In June 2004 GMP
became mandatory in China and the State Drug Administration announced that
local drug manufacturing establishments lacking approved GMP certifi cation would
not be allowed to continue the production of pharmaceuticals [22] .
The fi rst predecessors of manufacturing and quality requirements, which later
evolved into good manufacturing practices (GMPs), were issued in the 1940s in the
United States by the Food and Drug Administration (FDA) [1] . In the general
meeting of the World Health Organization (WHO) held in 1969, the World Health
Assembly issued a recommendation for the introduction of GMPs [2] . Since then,
most industrialized countries have passed laws on control procedures essential for
the manufacture of drug products. In some countries GMPs are integrated into
national legislation as a part of laws or regulations on production, distribution,
marketing, and use of drug products (GMP regulations). In other countries, GMPs
are separate guidelines outside the national drug legislation (GMP codes). In addition
to national GMPs, also some international organizations and trade blocks have
issued their own international GMP guidelines to harmonize the requirements for
drug production in different countries. However, regardless of their origin, the main
purpose of GMPs is to ensure that manufactured drug products have the safety,
identity, potency, purity, and quality that they are presented to have [3] . To fulfi ll
this aim, most GMPs usually cover quality management, personnel, premises, equipment,
documentation, materials management, production and in - process controls,
packaging and labeling of intermediate and fi nished products, laboratory controls,
validation, and change controls
NATIONAL GMP REGULATIONS AND CODES
2.1.2.1 United States
In the United States the production of drug products is controlled under the federal
Food, Drug and Cosmetic Act, which states that a drug product will be deemed to
be adulterated unless the methods used in or the facilities or controls used for its
manufacture, processing, packaging, or holding conform to or are operated or
administered in conformity with current GMP [5] . The actual GMP regulations are
issued as a part of the Code of Federal Regulations and as such they are a federal
law. The current set of GMP regulations is based on the 1978 revision [6, 7] of the
original GMP regulations, which were fi rst promulgated in 1963. The GMP regulations
are updated every year in April [8] ; however, no major changes have been
implemented since 1978. As an addition to GMP regulations, the FDA also publishes
other GMP - related guidance documents covering various issues of drug manufacturing
[9] . On the other hand, although these documents refl ect current views andexpectations of the agency, they only provide guidance on principles and practices
that are not legal requirements [1] . As a member of the International Conference
on Harmonization of Technical Requirements for Registration of Pharmaceutical
for Human Use (ICH), the United States has adopted the ICH guidance document
Q7, Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients, and
published it as a guidance for industry document [10] .
The U.S. GMP regulations are divided into two parts: 210 [6] and 211 [7] . Part
210, “ Current Good Manufacturing Practice in Manufacturing, Processing, Packing
or Holding of Drugs — General, ” provides the framework for the regulations [6] , and
Part 211, “ Current Good Manufacturing Practice for Finished Pharmaceuticals, ”
states the actual requirements. Part 211 is further divided into 11 subparts, which
cover the requirements for personnel, premises, equipment, control of materials,
production and process controls, packaging and labeling control, holding and distribution,
laboratory controls, documentation, and returned and salvaged products [7] .
The contents of Part 211 are presented in Table 1 .
2.1.2.2 Canada
The production of drug products (drugs) in Canada is controlled under the Food
and Drugs Act, which states that distributors and importers are not allowed to sell
a drug product unless it has been manufactured according to the requirements of
GMP. The principles of GMP are laid down by Division 2 in Part C of the Food and
Drug Regulations, which is a part of the Food and Drugs Act [11] . The Health
Products and Food Branch Inspectorate has also issued a guidance document (GMP
code), which has been prepared to assist in the interpretation of GMP regulations.
The current set of the Canadian GMP code was issued in 2002 and has not been
revised since. It has been written with a view to harmonization with GMP standards
of other countries and international organizations [WHO, Pharmaceutical Inspection
Cooperation Scheme (PIC/S), ICH]. Canadian Healthcare authorities have also
published several annexes to the basic GMP code covering topics such as GMP for
medical gases, biological drug products, blood products, and production of investigational
new drugs. In addition to the GMP code and its annexes, the Canadian2.1.2.4 East Asian Countries
Japan In Japan the production of drug products (drugs) is regulated under the
Pharmaceuticals Affairs Law (PAL), which states that any drug manufacturer who
plans to manufacture a drug product for sale in Japan must have a Japanese drug
manufacturing license and comply with Japanese GMP requirements. The fi rst regulations
of Japanese GMP were introduced in 1974 as The Standards for Manufacturing
Control and Quality Control . In 1979 PAL was partially revised and GMPs
became legally binding [2] .
PAL is managed and enforced via ministerial ordinances and notices, which are
detailed regulations prepared by the Japanese government. The requirements for
premises for drug manufacture are given in Ministry of Health, Labor and Welfare
(MHLW) Ministerial Ordinance No. 73, 2005 Regulations for Buildings and Facilities
for Pharmacies, etc. [originally Ministry of Health and Welfare (MHW) Ministerial
Ordinance No. 2, 1961] [17] , and the requirements for manufacturing and quality
controls in MHLW Ministerial Ordinance No. 95, 2003 Regulations for Manufacturing
Control and Quality Control of Drugs (originally MHW Ministerial Ordinance
No. 3, 1994). As a member of the ICH Japan has adopted the ICH guidance
document Q7, Good Manufacturing Practice Guide for Active Pharmaceutical
Ingredients , and published it as Pharmaceutical and Food Safety Bureau (PFSB)
Director - General Notifi cation No. 1200, 2001 Guidelines on GMP for Drug Substances
, which states the requirements for the manufacture of APIs. The requirements
concerning imported drug products are given in MHLW Ministerial Ordinance
No. 97, 2003 Regulations for Importing/Retail Management and Quality Control of
Drugs and Quasi - Drugs (originally MHW Ministerial Ordinance No. 62, 1999). The
requirements specifying manufacture of investigational products are given in PAB
Notifi cation No. 480, 1997 Products and Standards for the Buildings and Facilities of
Manufacturing Plants for Investigational Products (Investigational Product GMP)
[2] .
South Korea The production of drug products (drugs) in South Korea is regulated
under the Pharmaceutical Affairs Law, which was fi rst enacted in 1953 and has since
been revised several times [18] . New drug approval and related activities are regulated
in much the same way as in the United States and Japan. Korean GMP, which
is often called KGMP, was initiated in 1984 and became mandatory in 1995 [19] . A
drug manufacturer who intends to manufacture a drug product for sale in Korea
must have approval from the Commissioner of the Korea Food and Drug Administration
(KFDA). In order to require the license for manufacturing business the
manufacturer has to prove the compliance of facility standards with KGMP [20] .
China China regulates the production of drug products (drugs) under the Drug
Administration Law of the People ’ s Republic of China, which states that a drug
manufacturer has to conduct drug manufacture according to the GMP for pharmaceutical
products formulated by the Drug Regulatory Department under the State
Council on the basis of the Drug Administration Law [21] . In June 2004 GMP
became mandatory in China and the State Drug Administration announced that
local drug manufacturing establishments lacking approved GMP certifi cation would
not be allowed to continue the production of pharmaceuticals [22] .
No comments:
Post a Comment