Page 345 - Chiral Separation Techniques

338 13 International Regulation of Chiral Drugs

ommendations on acceptable methods for validating the characteristics of an analyt-
ical procedure. An indication of the data which should be provided in an application
for a marketing authorization is given. It discusses the following characteristics sep-
arately: specificity; linearity; range; accuracy; precision; detection limit; quantita-
tion limit; robustness and system suitability testing.

13.5.5 Common Technical Document

This ICH Topic (M4) is mentioned here as an indication of a future trend in the
global authorization of new medicinal products. It is probably the ICH’s most ambi-
tious undertaking, aiming as it does to provide the basis for a single set of registra-
tion documents to support an application for marketing authorization in any of the
three ICH regions. The EWG for the Common Technical Document (CTD) has been
extended to include the observers to ICH and representatives of the generics indus-
try and manufacturers of products for self-medication. There is also liaison with the
ICH topic (M2) on electronic submission of documents supporting a drug registra-
tion. The magnitude of the task is such that the progress to date on reaching a con-
sensus on the table of contents for the CTD has only been achieved after consider-
able debate. There are differences in regulatory practice in the three regions, in par-
ticular in the way that authorities interact with the drug development process, which
will provide considerable hurdles to be overcome by the harmonization process. The
CTD has been broken down into modules and the tables of contents (TOC) for the
quality, safety and efficacy sections have been released for Step 2 consultation. The
TOC give cross-references to appropriate harmonized guidelines. The CTD will pro-
vide the focus of the Fifth ICH Conference in November 2000.

13.6 The Effect of Regulatory Guidelines

The regulatory guidelines and attitudes of the regulatory authorities described above
have affected the number of submissions for authorization of medicinal products con-
taining drugs which are single enantiomers. Table 13-3 summarizes the data available
from various surveys [17–20] using the categories first established by Ariëns in 1984
[19]. The figures for the Medicines Control Agency (MCA) result from an informal
analysis of cases assessed between July 1996 and June 1999. Table 13-3 shows that the
proportion of synthetic chiral drugs developed as single enantiomers appears to have
genuinely risen between 1982 and 1999, even though the figures have been obtained
from different surveys. This increase reflects both the regulatory requirements intro-
duced in the early 1990s and the availability of the necessary scientific techniques to
synthesize and control the enantiopurity of chiral drugs. The proportion of synthetic
drugs which are presented in a nonchiral form is somewhat variable over the period of
time represented by the figures in Table 13-1. In the surveys conducted between 1982