The Drug development process - Pharmaceutical Biotechnology: Concepts and Aapplications - page 102

4.14.8 Mutual recognition

The mutual recognition procedure is an alternative means by which a marketing authorization
may be sought. It is open to all drug types except products of biotechnology. Briefl y, if this proce-
dure is adopted by a sponsor, then the sponsor applies for a marketing licence not to the EMEA,
but to a specifi c national regulatory authority (chosen by the sponsor). The national authority then
has 210 days to assess the application.
If adopted by the national authority in question, the sponsor can seek marketing licences in
other countries on that basis. For this bilateral phase, other states in which marketing authoriza-
tion are sought have 60 days in which to review the application. The theory, of course, is that no
substantive diffi culty should arise at this stage, as all countries are working to the same set of
standards as laid down in 'The Rules Governing Medicinal Products in the European Union'.
A further 30 days is set aside in which any diffi culties that arise may be resolved. The total ap-
plication duration is 300 days. If one or more states refuse to grant the marketing authorization
(i.e. mutual recognition breaks down), then the diffi culties are referred back to the EMEA. The
CPMP will then make a decision ('opinion'), which is sent to the European Commission. The
Commission, taking into account the CPMP opinion, will make a fi nal decision that is a binding.

4.14.9 Drug registration in Japan

The Japanese are the greatest consumers of pharmaceutical products per capita in the world. The
Ministry of Health and Welfare in Japan has overall responsibility to implement Japanese pharma-
ceutical law. Within the department is the Pharmaceutical Affairs Bureau (PAB), which exercises
this authority.
There are three basic steps in the Japanese regulatory process:

• approval ('shonin') must be obtained to manufacture or import a drug;

• a licence ('kyoka') must also be obtained;

• an offi cial price for the drug must be set.

The PAB undertakes drug dossier evaluations, a process that normally takes 18 months. The
approval requirements/process for pharmaceuticals (including biopharmaceuticals) are, in broad
terms, quite similar to the USA. The PAB have issued specifi c requirements (Notifi cation 243) for
submission of recombinant protein drugs.
Applications are initially carefully checked by a single regulatory examiner to ensure conform-
ance to guidelines. Subsequently, the application is reviewed in detail by a subcommittee of spe-
cialists. Clear evidence of safety, quality and effi cacy are required prior to approval.
In addition, the Japanese normally insist that at least some clinical trials be carried out in Japan
itself. This position is adopted due to, for example, differences in body size and metabolism of
Japanese, compared with US and European citizens. Also, the quantity of active ingredient present
in Japanese drugs is lower than in many other world regions. Hence, trials must be undertaken to
prove product effi cacy under intended Japanese usage conditions.