juridical person. The manufacturing or import
approval for a given drug is granted after ensuring
that the applicant is healthy and sane, legally com-
petent, and that the personnel, facilities and equip-
ments comply with the Pharmaceutical Law
requirements and quality standards in order to be
able to manufacture or import the approved drug
properly. The manufacturing approval is granted
for a specific drug to the facilities where the drug
will be manufactured. Manufacturing approval can
be transferred to legally authorized manufacturers,
for example through contracts or mergers.
In-country caretaker system
Approval might be obtained by either a domestic
company or directly by a foreign company settled
abroad, since the revision of the PAL in May 1983.
However, clinical data establishing efficacy and
safety should be generated in Japanese patients,
on Japanese territory; therefore, if the foreign com-
pany has no means of conducting these clinical
trials on its own, it should appoint an in-country
caretaker, domiciled in Japan. A clinical research
organization (CRO) is allowed to perform such
clinical development in respect to the PAL; the
CRO may be subject to spot inspections or other
specific requests from the MHLW, such as report
submission regarding ADRs. The CRO should be
able to take necessary measures to prevent the
occurrence or spread of health damages induced
by the drug under investigation (for more informa-
tion about CROs in Japan, please refer to Bentley,
1997).
Substances and devices regulated
by the PAL
Main groups defined by the law
Four groups are defined, which usually need an
Approval to be marketed in Japan, unless specifi-
cally designated by the MHLW:
- Drugs, including substances listed in the JP, sub-
stances for diagnosis, treatment or prevention of
human and animal diseases, and substances
affecting any structure or function of the human
or animal body. Apparatus or instruments are, of
course, excluded. This group can be divided in
prescription drugs (or ethical drugs) and non-
prescription drugs.- Quasi-drugs are substances that exert a mild
action on the body, such as drugs used to prevent
nausea, bad breath, body odor, hair loss, heat
rash and so on. - Cosmetics are substances also having a mild
action or no action on the body, but are for
external use, applied by rubbing or spraying
on the skin or hair, and are used for cleaning
or beautifying. - Medical devices are instruments or equipment
used for the diagnosis, treatment or prevention
of human or animal diseases. They are desig-
nated by ministerial ordinance.
Drug classificationThe four groups above include numerous sub-
classes, which vary according to the function of
different parameters: for example, approval pro-
cedures, approval authorities, handling of stan-
dards, list of data to be submitted. Regarding
drugs and data to be submitted for approval,
Figure 35.4 gives a good example of a possible
classification.Orphan drugsWithin the ethical drug class, a particular group
should be distinguished: orphan drugs. Orphan
drugs status was originally defined in 1993 as
follows: a drug is designated as orphan by the
MHLW after recommendation by the PAFSC,
when efficacy is scientifically established and
when it can benefit less than 50 000 patients.
Orphan drugs are subject to financial aid, priority
review and extension of the reexamination period
from 6 to10 years.35.3 DRUG DEVELOPMENT REGULATIONS OVERVIEW 493