the first approval of the new chemical entity. For
new indications and new formulations of a pre-
viously approved active agent, the data exclusivity
period is three years. These periods may be
extended by six months when the drug has under-
gone additional FDA-requested trials for pediatric
uses. Data exclusivity periods are only applicable
against a generic company that wants to rely on
another company’s drug as a reference; they do not
apply when the generic company has generated a
complete data package of its own.
The relevant data exclusivity periods for each
approved drug product, as well as any applicable
patents on the product or its use, are listed in the
‘Orange Book’, which is published by the FDA and
also available electronically on the FDA’s web site.
29.3 Generic approval process
outside the United StatesIn most countries, generic drugs may be approved
viaan abbreviated procedure similar to the ANDA
procedure in the United States. The applicant gen-
erally must show that the generic product has the
same dosage of the same active substance and the
same pharmaceutical form as the reference medic-
inal product. As in the United States, the applicant
must demonstrate bioequivalence to the reference
product.
All World Trade Organization (WTO) countries
are required under the General Agreement on Tar-
iffs andTrade (GATT) accordsto providesome sort
of registration data exclusivity periods. Europe has
data and marketing exclusivity rules which, in their
latest embodiment, preclude launch of a generic
product until 10 or 11 years after first approval of
the active substance. For products approved prior
to the new rules, there is six or ten years of data
exclusivity depending on the country. Approval
may be either through the regulatory agencies in
the individual countries orviaa central procedure.
In Japan, data exclusivity is normally six years for
new chemical entities. As in the United States,
clinical trials carried out by generic companies in
support of regulatory approval are excluded from
patent infringement in both the European Union
and Japan. However, there is no procedure in
Europe or Japan comparable to the US Orange
Book listing and Paragraph IV challenge procedure
described above. Consequently, patent holders
must usually wait until launch of an infringing
product to enforce their patents.
The relative strength of the generic industries in
various countries is largely a function of differ-
ences in government regulation of prices and
generic-for-branded substitution, as well as differ-
ences in the patent laws. In France and many south-
ern European countries, there are strict price
controls from the outset on the branded products,
so that the branded products are already relatively
cheap and there is less impact on price when the
patent expires. Brand loyalty also tends to be
relatively high, resulting in a large proportion of
‘branded generics’ products, which are not patent-
protected but rather sold as branded products by a
company other than the innovator. In Japan, the
prices for branded products are initially relatively
high, although prices are regulated down post-
launch. As the higher-priced branded products
are more profitable for pharmacists than generic
drugs and there are few incentives to substitute
generic drugs for branded drugs, the generic drug
industry in Japan is relatively small. In northern
Europe (e.g. the United Kingdom and Germany),
there are no price caps as such, but pricing is
strongly influenced by government reimbursement
levels, which are reduced when generics become
available, resulting in significant market share for
generic companies. The United States is the most
open of the large markets, with very high prices for
branded drugs, together with strong market incen-
tives on the part of pharmacies and insurance com-
panies to encourage generic substitution, resulting
in potentially very large profits for the first generic
on the market. Once there are multiple generic
products in the market, however, the intense com-
petition among generic companies results in rapid
and dramatic price erosion. Finally, the generics
industry is also strong in countries that have his-
torically had weak patent protection for pharma-
ceuticals. Although these countries are typically
poor and have low prices for branded and generic
pharmaceuticals alike, limiting the value of the
domestic market, these countries in some cases
provide a manufacturing base and launching pad384 CH29 GENERICS