E-DRUG: Major issue of the use of generic drugs in Japan
Generic drugs are said to be identical to the brand drugs in dose,
strength, route of administration, safety, efficacy, and intended use.
The use of generics in Japan is less than 10% at an amount-of-money
base. There seems to be several reasons why Japanese physicians are not
comfortable to prescribe generics even though MHLW (Ministry of Health,
Labour and Welfare) are trying to push the use of generics to reduce the
cost of health care. Let me summarize some examples obstacles to the use
of generics in Japan:
1. Different route of administration:
Diprophylline in the brand, for the treatment of heart failure or
bronchial asthma, could be administered sc, im or iv but one generic im
or iv and the other im only, leading to misuse of generics.
2. Different indication:
In the list of generics of one generic Co., there are about 40 drugs
with different indications, leading to make confusions to physicians
prescribing generic drugs.
3. Different pharmakokinetic parameters among each package insert:
Cmax of 100mg ticlopidine, an antiplatelet drug, is 390ng/ml in the
brand. Those of 12 generics are, 126, 141, 150, 179, 183, 189, 196, 239,
249, 258, 392 and 469 ng/ml.
Cmax of 2.5mg glibenclamide, a sulphonylurea antidiabetic, is 82ng/ml in the
brand. Those of 8 generics are, 53, 74, 89.6, 97.8, 98.7, 103, 126 and 144.1
4. Same pharmacokinetic parameters in 3 package inserts of generics:
All PK parameters (Cmax, AUC, tmax, t1/2) in 3 package inserts of 3
different generic companies show the same values after administrations
of 60mg loxoprofen sodium (NSAID) in 15 healthy male subjects each. From
a clinical pharmacological stand point of view, this is unbelievable.
5. Specifications, A stable supply, Information service:
MHLW gave 3 notifications on March in 2006 to rectify the present
situations in the next 5 years.
Concerning generics, there are another points of discussion which
include a) other ingredients not used in the brand, b) high levels of
impurities, c) Stress Testing and Long Term Testing not performed.
In order to contribute the reduction of the health care cost by generic
drugs in Japan, I would say that generic makers and regulatory
authorities have to secure users (doctors, pharmacists, patients,
etc) confidence by at least the following:
1. To revise different indications and different route of
administrations in some generics
2. To supply Clinical Safety Data
3. To analyse plasma concentrations and to calculate PK parameters by
the third party (ex. CRO)
4. To secure quality of generics in vitro dissolution test should be
performed by the authorized institute (ex. National Institute of Health
Sciences) before and after marketing at appropriate times
5. To report Organic Impurities, Inorganic Impurities and Residual
6. Ministry of Finance Japan should allow MHLW to get budget for the
quality control and quality assurance of the generic-drug policy.
Eiji Uchida, MD,PhD
Director, Clinical Trial Support Center, Showa University Hospital
Professor, Second Department of Pharmacology,
Showa University, School of Medicine,
Member of the Board of Directors, JSCPT
1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
Tel. +81-3-3784-8128, Fax. +81-3-3784-8129