To date, it is by no means clear that harmoniza-
tion has reduced the overall burden of regulations
for either the regulators or the regulated, but it has
already eliminated some inconsistencies. To those
ends, ‘Ethnic Factors Influence on the Acceptabil-
ity of Foreign Data’ was proposed by Japan and
Europe and accepted as an ICH 2 topic by the ICH
Steering Committee, Washington (24 March
1992). This chapter will give an account of the
ethnic issues faced by the working party, ending
in the tripartite implementation of the ‘Guidance’
of 1998. A working party made up of representa-
tives from each of three major regions was set up
and met many times for two-day working sessions.
A major study of approved drug dosage and phar-
macokinetics (PK) between the three regions was
undertaken by Japan’s MHWand JPMA. A further
study, commissioned by IFFPA, was undertaken by
the Centre of Medicines Research (CMR, UK). In
addition, the type and incidence of spontaneous
adverse events reports occurring with eight drugs
marketed in the European community were exam-
ined for consistency by the EC representative, and
concurrently, the data files of one pharmaceutical
company of four drugs in different therapeutic
areas was examined for any variations of PK,
dosage and adverse events between regions by
the EFPIA member. Only their major findings are
included in this chapter, more information can be
found in the individual reports [Naito and Yasuhara,
Walker and Harvey; Papaluca; Labbe ́; Edwards;
and Williams (ICH Orlando, 1993)].
Terminology
Race and Ethnicity are often used interchangeable
But the Office of Management and Budget (OMB)
issued in 1997 revised recommendations for the
collection of race and ethnicity data by Federal
Agencies. This led to the issue of a Guidance for
Industry (2005) by the FDA adopting the OMB
categorization.
The nonbinding recommendations were for the
US database if collected separately.
Racewould include American Indian/Alaska
Native, Asian, Black or African-American, Native
Hawaiian or Other Pacific Islanders. Ethnicity
would be Hispanic or Latino, or not Hispanic or
Latino.
If a combined format is used, then six categories
are recommended by adding Hispanic or Latino as
a group.
The agency admits that these are arbitrary
groupings and not based on anthromorphic, geneo-
logic or genetic grouping. Indeed if the evolution-
ary human tree was used as a guide, African, the
later evolving Asian/Mongaloid peoples and the
last to emerge Caucasians might be a better way to
define race. The word ethnicity could be used to
describe subgroups either genetic sub-variations or
culturally different – for example, Asian Indians
and Japanese – thus affecting ethnic ancestral
origins.
For the purpose of this chapter, the words race
and ethnicity will be used interchangeably.18.2 Regulatory practice
In the United States, initially, non-US studies, not
under the investigational new drug applications
(INDs), were considered primarily as a source of
supportive safety data. By the early 1970s, it was
appreciated that well-controlled non-US clinical
data could be utilized to support US new drug
applications. US regulations have allowed for the
use of non-US data as the sole basis for approval, so
long as certain conditions were met, including the
stipulation that ‘foreign data are applicable to US
populations and US medical practice’ (Food and
Drug Administration, 1975, 1985). No specifics
were given regarding the definition of ‘applicable’.
Thus, clinical data from phases I–III were allowed;
but in practice, such data could not be the sole
source of safety and efficacy for new drug
approvals. The reasons given for not using
Japanese data more widely in the United States
and Europe involve differences in medical prac-
tice, such as the use of different end points, lower
dosages, and differences in research methodology,
such as the emphasis on a large number of physi-
cians and their experience in phase III, resulting
in a large number of investigators with a low ratio
of patients enrolled. In Europe, although there
may be preference by individual countries to232 CH18 RACIAL AND ETHNIC ISSUES IN DRUG REGISTRATION