Fewer approvals for new molecular entities (NMEs) further highlight the innovation drought in small, nonbiological molecules.
An annual average of 22.2 NMEs was approved from 2000 to 2006, with only 18 NMEs being approved in 2005 and 2006 (see Figure
1). While these levels are above NME approvals from 1960–1980, they are below recent peaks. The average number of NMEs approved
in the 1960s was 13.7, 17.3 in the 1970s, 21.7 in the 1980s, 25.6 through 1990–1995 (2), and 32.2 from 1996 to 1999, led by
a recent peak of 57 in 1996.
Figure 1. Number of new molecular entities (NMEs) approved*
Survey respondents also identify shifting production patterns for APIs. Two-thirds of respondents expect the number of CGMP-compliant
API manufacturing facilities to increase in India (68%) and China (66%) during the next 5–10 years.
Industry estimates support this trend, particularly in the merchant market for generic APIs. In 2005, China and India supplied
57% of the generic APIs to Western Europe and 15–16% of generic APIs to the United States on a value basis, according to the
Chemical Pharmaceutical Generic Association (CPA, Milan, Italy). By 2010, India and China are expected to hold 67% of the
Western European market for generic APIs and 25% of the US market. The market share held by Indian API manufacturers in the
global API merchant market (both generic and innovator product) is expected to increase from 7% in 2005 to 10.5% in 2010 and
for Chinese API producers from 14% in 2005 to 22% in 2010 (3). For purposes of the analysis, APIs include both active ingredients
and advanced intermediates. 30
Looking back at the studies published in Pharmaceutical Technology, some of the major challenges facing formulation scientists during the past 30 years have remained fairly the same, including
enhancing the solubility of poorly soluble drugs, improving the stability of unstable drugs (e.g., proteins), controlling
and/or sustaining drug delivery, and ensuring accurate drug delivery to the intended target (4).
Throughout the years, formulation strategies also have had to adjust because of various political, ethical, and environmental
factors. The Montreal Protocol (1987) banned ozone-depleting ingredients from respiratory formulations, for example. And in
the late 1990s, vaccine makers faced increased pressures to formulate their products with no or at least reduced levels of
thimerosal, a preservative they had been using since the 1930s (5). As the number of new chemical entities declines, industry
continues its focus on preformulation, proof of concept (Phase 0) studies. And outsourcing formulation development is not
uncommon, even for Big Pharma companies that have formulation groups in house. In fact, our survey noted the growing impact
on the industry of outsourcing formulation development and manufacture.
With each decade, the formulator's toolkit has grown to address these challenges. For example, the traditional method when
working with poorly soluble drugs was to use water-miscible cosolvents. During the 1980s and 1990s, formulators experimented
with particulate carriers including liposomes and polymers as well as micro- and nanosized particle formation, emulsions,
novel spray drying methods, complex coating systems, protein precipitation, supercritical fluid technologies, improved milling
techniques, and crystallization (6). Formulation ingredients have changed as well. Thirty years ago, excipients were considered
"inactive ingredients," mainly fillers and binders purchased from chemical and food supply vendors. In contrast, the industry
now has a number of functional excipients, coprocessed excipients, and niche vendors who meet the needs of the pharmaceutical