Daniel I.C. Wang, MIT (Panel Chair)
Stephen W. Drew, Merck
Randolph T. Hatch, Aaston, Inc.
Arthur E. Humphrey, Lehigh University
Duane F. Bruley, University of Maryland Baltimore County
Stuart E. Builder, Genentech, Inc.
Marvin Cassman, National Institutes of Health
Alfred L. Goldberg, Harvard University
Nelson Goodman, U.S. Department of Agriculture
Frederick Heineken, National Science Foundation
Michael R. Ladisch, Purdue University
Oskar R. Zaborsky, National Research Council
The goals of the JTEC report on bioprocess engineering were to assess the status of bioprocess engineering and biotechnology, as well as to compare trends in the U.S. and Japan in areas relating to the biotechnological processes. The panel also sought to assess major differences between the U.S. and Japan in bioprocess engineering research and development.
In Japan, biotechnology activities occur primarily in large companies; few if any small biotech start-ups are apparent. Many Japanese companies with major efforts in biotechnology began in other fields of manufacturing. The product portfolio of the present Japanese biotechnology market is similar to that in the United States. Total sales increased 48 percent in 1990, to a total of $2.187 billion.
Japanese research in molecular biology and biological sciences is similar to that in the U.S. Japanese research is directed towards both prokaryotic and eukaryotic organisms. However, the panel did not notice any novel prokaryotic expression system under development in Japanese laboratories. Systems used for protein expression in prokaryotic organisms are similar to those employed in the United States. There is a very noticeable emphasis in Japan on research using eukaryotes, particularly in animal and mammalian cell systems. Lastly, the dominant opinion in Japan is that, for human therapy, murine antibodies will not be the major targets. Instead, humanized antibodies will be their choice.
Bioprocess engineering R&D philosophy in Japanese laboratories dealing with upstream technologies, such as recombinant protein production in bacteria and animal cells, differs from that in the U.S. The Japanese do not appear to emphasize the use of basic engineering principles for process development or process scale-up. Instead, the emphasis is much more biological, including screening, selection, and medium development. Also, automation in upstream technology is being developed extensively to reduce the human interface. One observation concerning Japan's upstream manufacturing technologies is the similarity to what they have acquired or licensed from the U.S. In the long run, Japan could move ahead of the U.S.
In downstream processing, the panel saw no new advances in product isolation and purification. Chromatographic media and methodology development is being carried out by Japanese companies that supply chemicals, biologicals, equipment and process expertise to the biomanufacturing sectors. There is noticeably intense activity in the area of in-vitro protein refolding. Many industrial laboratories have a heavy focus on protein refolding, but the panel learned little about their progress.
Research training and education for biotechnology and bioprocess engineering in Japanese universities is different from that in the U.S. Most Japanese research and educational programs are not driven by engineering principles and are located in other disciplines. Japanese university programs focus on applied research, which contrasts with the basic orientation of U.S. efforts. Lastly, the involvement of industrial and foreign investigators in Japanese university laboratories is extensive.
Bioprocess engineering R&D by Japanese companies is not driven by generic engineering principles, a situation similar to that found at Japan's universities. Process development activities are often performed directly at the manufacturing site rather than within the company's R&D laboratories.
Many Japanese government agencies support and perform basic and applied research in bioprocess engineering and biotechnology. The agencies help identify directions for Japan's biotechnology R&D. Government support for R&D is often long-range, with a typical planning horizon of ten years. The government has fostered development of an international network in advancing Japan's biotechnology program.
Japanese industry is focused on molecular biology efforts to use prokaryotic organisms for producing therapeutic proteins. Japanese industry has targeted recombinant products that the U.S. has already developed. It is evident that Japan plans to be a world player in the use of prokaryotes to compete in the pharmaceutical market.
The Japanese biotechnology industry has targeted animal cell cultures as vehicles for the production of therapeutic proteins. Due to their acquisition of U.S. cell culture processes, the Japanese are also in an excellent position to improve existing manufacturing methods. Japan's bioprocess engineering efforts will be competitive with and could even surpass those of the U.S. in the years to come.
There is a large research effort in Japan on protein engineering. However, the basic principles, software, and hardware presently employed are mostly from abroad. Japan has traditionally dominated many areas of bioprocess engineering and biotechnology; there is no sign that they have decreased their efforts in these areas. However, there is no counterpart when compared with the U.S. in the development of those potentials in biotechnology manufacturing systems. The Japanese biotechnology sector is rapidly entering into bioprocess manufacturing by using know-how either acquired or licensed from the U.S. This will reduce process development time and costs significantly, and speed Japan's market entry.
The JTEC panel prepared a qualitative comparison summarizing the present status and future trends in the U.S. and Japan in various areas relating to biotechnological processes (see Table 29).
-- Japan Compared to U.S. in Biotechnology Processes