Principles and Practice of Pharmaceutical Medicine

in 1996. New harmonized GCP standards are now
applicable to the United States, Europe and Japan
as well, but they require profound changes of the
Japanese system to be fully applied; the PAL had to
be amended in order to permit the enforcement of
the new GCP from April 1997. These had a major
impact on new study starts, the need for informed
consent being the largest reason.
The main changes for the Japanese clinic
(Takahashi and VandenBurg, 1997) include the
following:

New obligations for the sponsor, such as the
preparation of the clinical protocol and the writ-
ing of a clinical study report.

The abolition of the ‘chairman’ of the investiga-
tor steering committee (see Figure 35.5).

The designation by the medical institution of an
IRB which can be outside the hospital, such as an
academic society, and which will compulsorily
have a member from outside the institution.

The sponsor must establish an independent mon-
itoring system in order to conduct an adequate
evaluation of progress of the clinical trial, safety
information and efficacy end points. This means
that Japanese companies will now have to hire
medical doctors to handle medical matters.

The informed consent becomes awrittenconsent
and necessitates true and complete information

for the patient, including risk and compensation

for damage to the health of subjects.

The new GCP standards are, of course, similar

to those of the US and European GCP, to

which the reader should refer for detailed reg-

ulations.

The GPMSP. The PMS system is a well-estab-

lished system in Japan for collecting safety data in

order to prepare the documentation requested for

reexamination which will be described in the sec-

tion on ‘Post-approval activities’, below.

GPMSP standards were enforced in April 1994

after revision of the text published in May 1993. It

became a law in 1997, and was further revised in

2000, to add the ‘Early Post-Marketing Surveil-

lance’, applying to new drug in the first six months

of marketing. These standards specify the rules

to be observed by the manufacturer in order to

ensure the reliability of the PMS data, mainly the

following:

The manufacturer shall establish a PMS depart-

ment independent of the marketing division and

shall employ sufficient staff.

PMS managers shall prepare standard operat-

ing procedures for PMS in order to collect infor-

mation on drug use, assess this information and

take appropriate measures, undertake surveys

and special surveys when necessary, perform

post-marketing clinical trials, conduct self-

inspections, train and educate PMS personnel,

+ 1 government

controller

Central committee

of investigatiors

5 −10 Leaders

Investigators

(10, 50 or 100...)

Pharmaceutical

company Chairman

Figure 35.5 Clinical trials in Japan

35.3 DRUG DEVELOPMENT REGULATIONS OVERVIEW 497