Principles and Practice of Pharmaceutical Medicine

Quality standards for data, facilities
and functional organizations

These standards cover different fields describing
‘good practices’ ensuring the quality of the drug,
thequality and reliabilityof thedata generated with
the drug and, finally, warrant the efficacyand safety
of a given drug for a given disease, with respect to
scientific and ethical considerations for both
humans and animals.
GMP. Enforced in 1976, GMP establishes the
requirements ensuring drug production of a high
and constant quality. Ordinances 92 and 95, revised
in May 2003, contain guidance on the following:

Manufacturing control and quality control
(GMP software).

Duties of the Control Manager (self-inspection,
education and training, etc.).

Standards for buildings and facilities for manu-
facturing plants (GMP hardware).

In 1988, GMPs for medical devices were also
enforced. A group of inspectors attached to pre-
fectorial government perform regular on-site
inspections of manufacturers, importers and dis-
tributors in order to check their compliance to
GMP.
GMP compliance certificates for Japanese drug
plant have been issued since 1982; today bilateral
agreements have been signed with the United
States and EU since May 2003, with regard to
GMP compliance recognition.
Regulations for Imported Drug Management
and Quality Control. Also related to drug quality,
the standards for Quality Assurance of Imported
Drugs and Medical Devices were notified in 1993,
establishing basic quality assurance requirements
with which the drug importer should comply. The
MHLWordinance 62 of June 1999 today regulates
drug import to Japan.
GLP. In order to ensure the reliability of animal
data, GLP standards were published by the PAB in
March 1982, enforced one year later and revised in
October 1988. GLP describes standards for person-
nel and organization (management, quality assur-

ance unit, etc.) for animal care facilities and

equipment, standard operating procedures for the

operation of testing facilities, test and control arti-

cles, the conduct of a study, the study report, and

the storage of the raw data.

These standards originally concerned animal

safety studies; today, they are applied to all animal

studies, for example, toxicology, pharmacology

and animal PK. GLP was legalized as an MHLW

Ordinance in 21 March 1997, requiring in particu-

lar to establish SOPs and the preparation of proto-

cols and study reports. PMDA is conducting GLP

compliance reviews and on-site inspections of

testing facilities.

GLP applies to foreign data when attached to the

NDA. Mutual GLP agreements have been signed

between Japan and the United States, EU and

Switzerland.

GCP. Written in 1985, Japanese GCP standards

were notified by the MHLW in 1989 for a general

application from October 1990. They laid down

rules for conducting a clinical trial properly from

an ethical and scientific standpoint:

Definition of the respective role and responsibil-

ities of the sponsor, the investigator and the

medical institution.

The contract for a clinical trial between the

sponsor and the hospital conducting the study.

The institutional review board (IRB) in each

medical institute, its role and organization.

The informed consent of patient to participate

into the trial, which was not originally a ‘written’

consent.

The storage of the study records (source data)

during a certain period of time.

These rules, however, were to be applied to a

clinical development organization specifically in

Japan, and were very different from our Western

ones (cf. section on ‘Clinical Development’,

below). Within the framework of the International

Conference on Harmonization (ICH), GCP were

re discussed for several years and finally concluded

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