In terms of regulatory organization, respondents felt that the formation of the European Union, which led to one European
Pharmacopeia, had the greatest impact on pharmaceutical manufacturing (67%) since 1977 as compared with actions such as the
reorganization of the Center for Drug Evaluation and Research (CDER) and the Center for Biologics Evaluation and Research
(CBER) (46%). The EU's creation allowed manufacturers to prepare a single submission package for new drugs or devices rather
than one for each country. In addition, the EU provided a balance to global regulatory power. The EU "allowed for a second
major voice in defining policy and practice for pharmaceutical business," said one respondent. The creation of the International
Conference on Harmonization (ICH) in 1990 was also toward the top of the list of important regulatory organization actions,
with 61% listing ICH as having "high" or "some" impact.
Looking forward, survey results showed an overwhelming trend toward going global. Out of a list of 11 factors, including wireless
technology and green chemistry, respondents overwhelmingly (83%) ranked globalization as the prime factor to have an impact
on the future direction of pharmaceutical manufacturing. This was true across all fields. Not surprisingly, 71% of respondents
predicted the practice of outsourcing to increase in the next 5–10 years. This statistic was ahead of 21 other factors, including
Big Pharma consolidation (51%) and the number of combination products (58%). Specifically, a majority of participants felt
the number of CGMP-compliant manufacturing facilities would increase in both China and India in the next 5–10 years.
Whether these changes will improve relations between the regulatory authorities and industry is unclear. Only a small majority
of survey respondents (53%) thought collaboration between FDA and industry would increase in the next decade. Either way,
with so many trends pointing abroad, it's inevitable that ICH will have to expand. If outsourcing is to increase as survey
participants suggest, common regulatory standards and policies will be necessary to make such partnerships easier and more
With greater scrutiny comes greater analysis. Or so it seems when we review the advances in analytical technology. FDA mandates
have most famously influenced the process of discovery, but more and more, regulations governing the manufacture of drugs
are being regulated. Now, rather than guaranteeing that the finished drug emerging from manufacturing and into the market
is perfect, each step in the process itself has to hew to certain standards.
With regard to improvements in techniques, the most prominent new technique during the past 30 years is high-performance liquid
chromatography (HPLC). Until the late 1970s, most pharmaceutical analysis was conducted through wet-chemistry testing, and
few stability-indicating assays were available. Different drugs required different release-testing techniques. After HPLC
testing became a viable option, it gained popularity for its speed and accuracy. The technique also brought uniformity to
release testing. HPLC testing has now become the industry standard.
Near-infrared (NIR) spectroscopy is another technique to emerge within the past 30 years. The method and technology evolved,
and NIR was introduced to manufacturing facilities. Now NIR is used to quantify materials online.
Atmospheric mass spectrometry (MS) is now widely used, but was unavailable 30 years ago. MS instruments were previously very
large and could only be operated by specialists. The instruments required pressurization, and samples had to be introduced
one at a time. But today's MS instruments are much smaller, with some models even fitting on the benchtop.
In the automation field, computers have profoundly changed analytical testing. Calculations are no longer performed by hand
but by computers and software. Quantification has become more uniform, and accurate results can be obtained more quickly.
Testing and sample preparation are now automated as well, eliminating human imprecision and making results more accurate and
FDA's process analytical testing (PAT) initiative has been another major influence in analytical testing. The program, initiated
in the 1990s, should require manufacturers to collect and analyze data to demonstrate control over their processes. The data
must show that the processes will generate results within acceptable specifications. The initiative incited companies to seek
real-time analytical results and underscored the need for centralized process data. Manufacturers began focusing tests on
characteristics related to product performance, and techniques have shifted toward direct rather than indirect measurement.
As testing moved upstream, manufacturing divisions began to perform analytical testing. Quality-assurance personnel now concentrate
on auditing test results and ensuring test methods are validated.