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タイトル Industrial Technological Trajectories and Corporate Technology Title Traditions : The Development of Antibacterial Drugs in Japan 著者 Hara, Takuji Author(s) 掲載誌・巻号・ページ The Annals of the School of Business Administration, Kobe Citation University,41:1-18 刊行日 1997 Issue date 資源タイプ Departmental Bulletin Paper / 紀要論文 Resource Type 版区分 publisher Resource Version 権利 Rights DOI JaLCDOI 10.24546/81003680 URL http://www.lib.kobe-u.ac.jp/handle_kernel/81003680

PDF issue: 2021-09-29 Industrial Technological Trajectories and Corporate Technology Traditions: The Development of Antibacterial Drugs in Japan*

Takuji Hara

I. Introduction

We have to consider two levels of the path of technology, when we talk about the technological change of a firm. One is the industrial technological trajectory' which is historically observed in the industry as a whole. The other is the corporate technology tradition' (CTT) which is seen in an individual company. A clarification of industrial technological trajectories and corporate technology traditions is very useful for elaborating the theory of industrial technological change and for drawing practical implications for the management of technology. There are, however, few empirical studies of industrial techno- logical trajectories or corporate technology traditions. One of the rare studies is Achilladelis' study (1993) of the technological innovation in the sector of antibacterial medicines. He found four technological trajectories in that sector, namely, sulphonamides, natural product , semisynthetic antibiotics and synthetics. The most active period of each trajectory was the 1930s, the 1940s-1950s, the 1960s-1970s, and the 1980s-1990s respectively. He also found corporate technology traditions in some companies. For example, Upjohn, Pfizer and Lilly had CTTs in natural products antibiotics, Pfizer and Lederle had them in tetracyclines, Beecham and Bristol had them in semisynthetic , and Glaxo and Lilly had them in . According

* The funding for this study was provided by the Japan Ministry of Education , Science, Sports and Culture (grants 08730071). 1. This is based on the concept of natural trajectory developed by Nelson and Winter (1977). However, we do not use their terminology because the words "technological trajectory" make the concept more concrete . Similarly, we do not use the concept of technological paradigm promoted by Dosi (1982), because any technological change in this case can be described without the concept. 2. This concept comes from Achilladelis (1993). He defined corporate technology tradition as the "concentration of a company's R & D resources on a particular technology for very long periods of time leading to the introduction of many innovations embodying this technology." (p. 281) 2 T. Hara

to him, early entries with a radical innovation which was commercially very successful have led to the development of CTTs in antibacterial medicines. He also stated that CTTs are usually confined within a single technological trajectory, and that CTTs may extend over two successive trajectories when the two trajectories share some characteristics, or when the new technology can be easily appropriated. This study will develop Achilladelis' study into a more-detailed one and add more consideration of the construction process of industrial technological trajectories and corporate technology traditions. For this, we choose the development of antibacterial drugs as a research site like Achilladelis, although ours is limited only to the Japanese experience. The observation of the experience of a certain nation may produce another benefit, that is, the opportunity for international comparison. We may be able to derive some characteristics of the technological change of Japanese pharmaceutical firms, which were latecomers to the world pharmaceutical industry. In the next section, we will describe the case of the development of antibacterial drugs in Japan. In Section Three, we will interpret this case and extract some hypotheses. In the final section, we will point out some implications of this study and some issues for further study.

II. The Development of Antibacterial Drugs in Japan

It is since the middle of the 1960s that Japanese firms have become active in the development of antibacterial drugs. Although some antibacterial drugs were developed before the middle of the 1960s, for example, kanamycin (discovered in 1957, commercialized in 1958) and fradiomycin (discovered in 1948, commercialized in 1960) by the Hamao Umezawa group, leucomycin (discovered in 1953, commercialized in 1957) and mitomycin (discovered in 1956, commercialized in 1964) by the Hata group of the Kitasato Institute and (discovered in 1950, commercialized in 1957) by Yasuo Koyama, they were developed mainly by researchers in universities or academic institutes. Pharmaceutical firms also developed some antibacterial drugs in the early 1960s. Sulfamethoxazole, commercialized in 1960 by Shionogi, and sulf a- monomethoxine, commercialized in 1961 by Daiichi, both of which were effect-lasting types of sulphonamide, are examples of those drugs. However, most of the antibacterial drugs of Japanese origin were Industrial Technological Trajectories and Corporate Technology Traditions 3

developed after the middle of the 1960s by firms. Therefore, we concentrate our analysis on the period since that time. Table 1 presents the antibiotics and synthetic antibacterial drugs of Japanese origin which were given approval for manufacturing by the Ministry of Health and Welfare (MHW)3 from 1967 to 1994. By categorizing these data and observing them historically, we can find at least five characteristics of the development of antibacterial drugs in Japan.

Table 1: Antibacterial drugs developed in Japan (1967-1994)

Year of Medicine Production Chemical name Trade name Company Drug family approval form method bekanamycin sulfate Kanendomysin Meiji aminoglycoside 69. 04. injection natural p. enramycin * * * not sold * ** Takeda peptide 70. 01. natural p. josamycin Josamaycin Yamanouchi macrolide 70. 01. oral use natural p. sodium Cefamejin Fujisawa chphem 71. 04. injection semi syn. ribostamycin sulfate Vistamycin Meiji aminoglycoside 72. 08. injection natural p. piromidic acid Panacid Dainippon synthetic 72. 08. oral use syn. sulcenicillin sodium Lilacillin Takeda 72. 08. injection semi syn. midecamycin Medemycin Meiji macrolide 73. 01. oral use natural p. dibekacin sulfate Panimycin Meiji aminoglycoside 74. 07. injection semi syn. bleomycin sulfate Bleomycin Nihon-kayaku anticancer 74. 09. injection natural p. josamycin propionate Josamy-drysyrup Yamanouchi macrolide 75. 01. oral use semi syn. propionylmaridomaycin * * * not sold * * * Takeda macrolide 75. 01. semi syn. enviomycin sulfate Tuberactin Toyo-jyozou peptide 75. 04. injection natural p. amikacin sulfate Amikacin Banyu aminoglycoside 76. 08. injection semi syn. neocarzinostatin Neocarzinostatin Kayaku anticancer 76. 08. injection natural p. Yamacillin Yamanouchi 77. 03. oral use semi syn. hydrochloride penicillin ceftezol sodium sodium (Fujisawa) 77. 08. injection semi syn.

pivmecillinamh Melysin Takeda penicillin 78. 05. oral use semi syn. ydrochloride pipemidic acid Dolcol Dainippon synthetic 78. 08. oral use syn. sodium Pentcillin Toyama penicillin 79. 05. injection semi syn. sodium Cefmetazon Sankyo cephem 79. 08. injection semi syn. Pansporin Takeda cephem 80. 10. injection semi syn. dihydrochloride sodium Takesulin Takeda cephem 80. 10. injection semi syn. peplomycin sulfate Pepleo Nihon-kayaku anticancer 80. 10. injection semi syn. minronomycin sulfate Sagamicin Kyowa aminoglycoside 81. 09. injection natural p. sodium Cefoperazin Toyama cephem 81. 09. injection semi syn. sodium Shiomarin Shionogi oxacephem 81. 12. injection semi syn. sodium Epocelin Fujisawa cephem 81. 12. injection semi syn.

Bestcall Takeda cephem 82. 10. injection semi syn. hemihydrochloride

3. As is generally known, there is a seven to ten year gap between the discovery of a drug and its approval. In this study, we operationally regard the year of approval as the year of development. 4 T. Hara

Trade name Company Drug family Year of Medicine Production Chemical name approval form method sodium Yamatetan Yamanouchi cephem 83. 05. injection semi syn. norfloxacin Baccidal Kyorin synthetic 84. 02. oral use syn. astromycin sulfate Fortimicin Kyowa aminoglycoside 85. 04. injection natural p. sodium Tomiporan Toyama cephem 85. 04. injection semi syn. sodium Suncefal Yamanouchi cephem 85. 04. injection semi syn. midecamycin acetate Miocamycin Meiji macrolide 85. 04. oral use semi syn. ofloxacin Tarivid Daiichi synthetic 85. 04. oral use syn. enoxacin Flumark Dainippon synthetic 85. 08. oral use syn. sodium Ajicef Ajinomoto cephem 86. 09. injection semi syn. rokitamycin Ricamycin Toyo-jyozou macrolide 86. 09. oral use semi syn.

lenampicillin Varacillin Kanebo 86. 09. oral use semi syn. hydrochloride penicillin aspoxicillin Doyle Tanabe penicillin 87. 03. injection semi syn. Cefspan Fujisawa cephem 87. 06. oral use semi syn. pivoxil Tomiron Toyama cephem 87. 06. oral use semi syn. sodium Cosmocin Lederle(JP) cephem 87. 06. injection semi syn. sodium Meicelin Meiji cephem 87. 06. injection semi syn. sodium Amasulin Takeda 87. 10. injection syn. sodium Flumarin Shionogi oxacephem 88. 03. injection semi syn. injection, pirarubicin Pinorubin (Sanraku) anticancer 88. 03. oral use semi syn. proxetil Banan Sankyo cephem 89. 09. oral use semi syn. lomefloxacin Bareon Hokuriku synthetic 90. 01. oral use syn. hydrochloride cefotiam hexetil Pansporin T Takeda cephem 90. 03. oral use semi syn. hydrochloride arbekacin sulfate Habekacin Meiji aminoglycoside 90. 09. injection semi syn. Cefzon Fujisawa cephem 91. 10. oral use semi syn. Seftern Shionogi cephem 92. 10. oral use semi syn. fleroxacin Megalocin Kyorin synthetic 93. 07. oral use syn. sparfloxacin Spara Dainippon synthetic 93. 07. oral use syn. betamipron Carbenin Sankyo 93. 10. injection syn. zinostatin stimalamer Smancs Yamanouchi anticancer 93. 10. injection semi syn. levofloxacin Cravid Daiichi synthetic 93. 10. oral use syn. pivoxil Meiact Meiji cephem 94. 04. oral use semi syn.

Source: Ministry of Health and Welfare (1995), pp.275-398; Fukai (1988, 1995); Yakuji-nippou (1967-1995); Tatsuta and Yagisawa (1994).

First, we can identify clearly industrial technological trajectories. Figure 1 shows the transition of the composition of the types of drugs, categorized in terms of their production methods. In the period 1970- 74, more than half of the drugs developed were natural products, but natural products decreased clearly after that period and reached nil in the period 1990-94. Semisynthetic antibiotics were the mainstream from the period 1975-79, and reached a peak in the period 1985-89, then declined in the period 1990-94. Synthetic antibacterial drugs have been steadily increasing, and were nearly equal to semisynthetic antibiotics in the period 1990-94. Thus we can see the clear shift of technological Industrial Technological Trajectories and Corporate Technology Traditions 5

trajectories: from natural products through semisynthetics to complete synthetics.

Figure 1: Transition in the kind of antibacterial drugs developed in Japan

Secondly, there seems to be another kind of shift of technological trajectories. Figure 2 shows the transition of the composition of the medicine form in cephalosporins. According to this, though all of the drugs developed until the period 1980-84 were for injection, there was an emergence of cephalosporins to be taken orally in the period 1985- 89. In the period 1990-94, all of the drugs developed were for oral use. This suggests that there are at least two dimensions of technological trajectories of antibacterial drugs: trajectories in terms of the

Figure 2: Transition in the method of consumption (cephem) 6 T. Hara

production methods and those in terms of the methods of consumption of the drugs. Thirdly, when we classify the drugs in terms of a family of drugs such as the aminoglycoside family, the macrolide family or the cephem family, we can see that only a small number of companies have developed drugs in each family. Figure 3 shows this. The top company in the development of each drug family occupies a very large share of the number of drugs developed. For example, the top companies occupy more than 40 percent in the aminoglycoside family, the peptide family, anticancer antibiotics and synthetic antibacterial drugs. Even in the cephem family which is the least oligopolized, the top company Fujisawa has developed more than twenty percent of the drugs. Two companies developed all the drugs in the peptide family, three did all in the aminoglycoside family and anticancer antibiotics, four did all in the macrolide family and synthetic antibacterial drugs and five did all in the penicillin family. From these observations, we can say that a small number of companies has developed the drugs in a certain family.

Fourthly, we identify clearly corporate technology traditions in the field of the development of antibacterial drugs. Table 2 presents the categories of antibacterial drugs developed by each company. Seven of the thirteen companies developed drugs in only one category: Kyouwa in the aminoglycoside family, Fujisawa and Shionogi in the cephem Industrial Technological Trajectories and Corporate Technology Traditions 7

family, Nihon-kayaku in anticancer antibiotics, and Dainippon, Daiichi and Kyorin in synthetic antibacterial drugs. Furthermore, three of the four drugs developed by Toyama, two of the three by Sankyo and four of the nine by Takeda belong to the cephem family'. If we do not take the production method into consideration, four of the nine drugs developed by Meiji are in the aminoglycoside family. Thus, most of the drugs developed by a certain company are likely to belong to one category and we can regard this as being a corporate technology tradition.

Table 2: Categories of antibacterial drugs developed by each company

Anticancer Synthetic Natural antibiotics Semisynthetic antibiotics Total antibiotics antibacterial drugs

amino- amino- synthetic peptide macrolide penicillin macrolide cephem anticancer quinolone glycoside glycoside antibiotics

Meiji 2 1 2 1 2 1 9

Kyowa 2 2

Toyo-jyozo 1 1 2 Takeda (1) 2 (1) 4 1 7(9) Yamanouchi 1 1 2 6

Fujisaw a 5 5 Shionogi 3 3

Toyama 3 4

Sankyo 2 1 3 Nihon-kayaku 2 2

Dainippon 4 4

Daiichi 2 2

Kyorin 2 2 * The drugs in parentheses were approved but were not sold.

Finally, some companies have developed antibacterial drugs in more than one category. For example, Meiji and Yamanouchi developed both natural products and semisynthetic antibiotics. This indicates that a company can have a technology tradition which extends over more than one different technological trajectory. However, it is also the case that no company which has developed antibiotics has also developed

4. Both the penicillin family and the cephem family belong to the beta-lactam family. Broadly speaking, therefore, we can say that all the drugs developed by Toyama and six of the nine drugs ( six of the seven that were commercialized ) developed by Takeda belong to the beta-lactam family. Yamanouchi developed three beta-lactam family drugs and two macrolide family drugs. 8 T. Hara

synthetic antibacterial drugs. There may be some reasons for these phenomena. We will consider them in the next section.

III. Discussion

Industrial technological trajectories and corporate technology traditions were found in the development of antibacterial drugs in Japan. But how were they formed? Were there any differences between Achilladelis' explanation and the Japanese case? We will consider these points in this section. The technological trajectories in Japan are almost the same as those in Western countries, though there was a time lag. This suggests that technological trajectories are transferable. Indeed, as we will see below, most of the technologies in the Japanese antibacterial drugs sector did not originate in Japan but were transferred from Western countries. We, therefore, consider technological trajectories in general. The beginnings of the technological trajectories of antibacterial drugs seem to be varied: Achilladelis (1993) said that the first sulphonamide "was introduced under perfect conditions for a successful innovation" while the first natural "was a serendipitous discovery under conditions commonly associated with innovation failures" and that the first semisynthetic penicillin was developed after nearly ten years of dogged research by Dr. J. C. Sheehan's group. Though the beginnings were different, each of them was followed a group of products which had similar characteristics. The reason for the formation of a series of product innovations is likely to be related to the method of organizational searching. Practical searching for solution by companies does not follow optimal standards but satisfactory standards. Nelson and Winter (1977) insisted that the development of technology by firms also follows this kind of rule. They observed that a specific method for developing technology was used continuously for a certain period. The screening of soil samples, in the case of natural antibiotics, and the modifying of existing drugs, in the case of semisynthetic antibiotics, are examples of such methods. As long as companies can develop new and better drugs by an existing method, they continue to use the method. That is the reason for the formation of a technological trajectory. Next, we should consider the reason for a shift between different Industrial Technological Trajectories and Corporate Technology Traditions 9 technological trajectories. First, as Achilladelis (1993) mentioned, the shift is likely to stem from the limits of technological progress. In the case of antibacterial drugs, difficulty in the development of stronger, broader or safer drugs by an existing method was one of the main limits. The acquisition of resistance to existing drugs by bacteria was also such a limit. Secondly, technological opportunity is also a prerequisite of a shift. If it had been impossible to synthesize antibiotics, the shift from natural antibiotics to synthetic ones would not have occurred. Thirdly, economic rationality is also likely to affect a shift. After the synthesis of antibiotics had become economically feasible, synthetic antibiotics became more appropriate for mass production than natural products. This economic reason is likely to underlie the shift from natural products to semi- or full- synthetic drugs. Finally, the voice of demand may cause a shift. The shift from drugs taken by injection to drugs for oral use in the cephem family may have been promoted by demands for an easier method of taking the drugs. Thus, we consider that the main factors which affect the shift between different technological trajectories are technological limits, technological opportunities, economic rationality and the demands of the market. Now we move our focus to corporate technology traditions. As Achilladelis (1993) found CTTs in Western companies, so we were able to find them in Japanese companies. Achilladelis (1993) said that early entries with a radical innovation which was commercially very successful had led to CTTs in antibacterial medicines. But this seems to be neither a sufficient explanation nor one that is generally applicable. In Japan, radical innovations in antibacterial drugs have not been so common'. We should consider other reasons for the formation of CTTs in Japan by using some "circumstantial evidence." The first clue is in Table 3, which presents the important technology licensing contracts between Western companies and Japanese companies for antibacterial drugs. Meiji and Kyouwa were the first Japanese licensees for making streptomycin, a representative drug of the aminoglycoside family. Fujisawa got a production license for C in 1961 from the UK National Research

5. One of the few exceptions was norfloxacin, the first "new-quinolones" family of synthetic antibacterial drugs, which was developed by Kyorin. 10 T. Hara

Development Corporation, which was promoting the commercialization of cephalosporins developed by a research team in Oxford University. Takeda signed a joint research and development contract with Ciba- Geigy in 1970 and came to be supplied with 7-ACA, the basic material of cephalosporins, by that company. Daiichi received the technology for making nalidixic acid, the first quinolone-type synthetic antibacterial drug, from Winthrop in 1964. These Japanese companies constructed their CTTs with the technology introduced from foreign companies. Therefore, we can regard technology licensing as a factor in the making of CTTs.

Table 3: Important licensing agreements made by Japanese companies in antibacterial drugs

Year of Drugs Category Licenser Licensee licensing

streptomycin aminoglycoside Merck Kyowa-hakkou, Meiji 1951 chloramphenicol others Parke-Davis Sankyo 1951

benzyipenicillin Wyeth Banyu 1953 benzatine penicillin

American tetracycline tetracycline Takeda (Lederle JP) 1953 Cyanamid

chloramphenicol others Bohringer Yamanouchi 1954 tetracycline tetracycline Bristol Banyu 1955 Ilolotycin macrolide Eli Lilly Shionogi 1957

semieynthetic Syncillin Bristol Banyu 1960 penicillin cephalosporin cephem UK NRDC Fujisawa 1961 nalidixic acid synthetics Winthrop Daiichi 1964 cephalosporin cephem Ciba-Geigy Takeda (joint R&D) 1970

Source: Nihon Yakushi Gakkai (1995), p. 111 and the documents of each company.

Secondly, collaboration with universities or public research institutes may be another factor in the making of CTTs. For example, Nihon-kayaku commercialized bleomycin, an anticancer antibiotic, through collaboration with the Umezawa group. Toyama succeeded in the production of a semisynthetic penicillin through collaboration in 1971 with the Ishimaru group of Osaka University. The company applied that technology to the development of cephalosporins. Toyo- Industrial Technological Trajectories and Corporate Technology Traditions 11

jyouzou commercialized a macrolide antibiotic, kitasamycin, developed by the Hata group of the Kitasato Institute. Meiji collaborated with Dr. Umezawa to develop an aminoglycoside antibiotic, kanamycin. Thus, research collaboration with various research institutes may be another reason for the emergence of CTTs. Finally, there is a case in which complementary assets (Teece, 1987), such as a production system or a distribution network, may facilitate the construction of a CTT. For example, Shionogi has a long- term relationship with Eli Lilly, which has a strong CTT in cephalosporins. Shionogi has produced and sold the cephalosporin medicines developed by Eli Lilly, such as Keflin, Keflex, Kefral and Kefdole, for a long time. From this, Shionogi was likely to have been able to accumulate the complementary assets suitable for the development of cephalosporins. Shionogi's late entry into the field of development of the cephem antibiotics may imply that this was the reason. Now, we know that there may be several reasons for the emergence of CTTs: technology licensing, collaboration with research institutes and the establishment of complementary assets. But, why do the CTTs persist for a fairly long time? We can consider some factors that may cause this phenomenon. The first factor is, again, the organizational routine of each company. Each company has its own scope of searching problems and solutions. Because the scope is path- dependent, once a CTT is established, a company acquires a specific network of technological problems and solutions, and this makes the CTT durable. The second factor is the scarcity and specificity of corporate research and development resources. It is well known that developing a drug costs a company an enormous amount of money. Furthermore, special skills and knowledge are likely to be necessary for the development of drugs'. It is, therefore, difficult economically and intellectually for a company to have various technology traditions in the field of antibacterial drugs alone. The third factor is the rationality of risk aversion. There exists a huge uncertainty and a large risk in the development of drugs. In Japan, only one in over 2000 drugs discovered receives an approval for

6. Henderson and Cockburn (1994); Gambardella (1995), Chapter 3. 12 T. Hara manufacturing. A failure in development means a serious loss. It is essential for a company to avoid the risk of a failure. Developing drugs in a familiar area provides more certainty than the developing of them in an unfamiliar field. Therefore, it seems to be rational for a company to develop drugs in an existing technology tradition if this is profitable. There seem to be some other factors. Complementary assets may be one of them. Utilizing existing complementary assets is much less expensive than building new ones. It is rational for a company to try to use existing complementary assets if the opportunity costs are not prohibitively high. Other possible factors are institutional. For the period of the data in Table 1, Japan MHW reduced drug prices consistently. If a company wants to keep its revenue under these conditions, it has to replace existing drugs with new ones which have similar characteristics. This may foster an existing CTT. Moreover, patents or other regimes of appropriability may inhibit a company from entering other technological fields. This may limit the dispersion of a CTT. Lastly, the commercial success of a drug developed previously by a company may reinforce a CTT. Table 4 shows the estimated market size for each antibacterial medicine produced in Japan from 1985 to 1995 in Japan. Fujisawa's Cefamezin (cephem), Yamanouchi's Josamycin (macrolide), Toyama's Pentcillin (semisyn- thetic penicillin) and Cef operazin (cephem), Sankyo's Cefmetazon (cephem), Takeda's Pansporin (cephem), Shionogi's Shiomarin (oxace- phem), Kyorin's Baccidal (synthetic), Daiichi's Tarivid (synthetic) and Dainippon's Flumark (synthetic) were all successful in the market and probably contributed to the establishment of the technology tradition in each company. In sum, corporate technology traditions which stemmed from a licensing agreement, a research collaboration and/or an accumulation of complementary assets were reinforced by organizational routines, resource scarcity and specificity, risk aversion, specific complementary assets, institutional factors and/or past commercial successes. That is the probable process of the establishment of CTTs. Achilladelis (1993) argued that CTTs may extend over two successive trajectories when the two trajectories share some characteristics, or when the new technology can be easy appropriated. In the Japanese case, the CTTs of Meiji and Yamanouchi extend over Industrial TechnologicalTrajectories and Corporate TechnologyTraditions 13

Table 4: Estimated market size of antibacterial medicines (1985-4995) (hundred million yen)

Year of Trade name Company 85 86 87 88 89 90 91 92 93 94 95 approval

Josamycin Yamanouchi 1970 30 25 60 50 Cefamezin Fujisawa 1971 190 280 215 150 140 140 150 180 220 220 180 Lilacillin Takeda 1972 50 60 Panimycin Meiji 1974 100 60 60 30 20 30 Amikacin Banyu 1976 50 20 20 Yamacillin Yamanouchi 1977 20 Pentcillin Toyama 1979 75 210 225 200 170 180 190 170 150 120 90 Cefmetazon Sankyo 1979 240 365 300 250 200 180 180 130 80 60 70 Pansporin Takeda 1980 250 500 500 430 350 350 380 350 260 250 240 Takesulin Takeda 1980 70 50 Cefoperazin Toyama 1981 110 310 245 150 130 20 Shiomarin Shionogi 1981 300 500 530 450 270 210 130 70 30 20 Epocelin Fujisawa 1981 160 270 260 200 170 150 100 Bestcall Takeda 1982 120 210 200 120 100 80 Yamatetan Yamanouchi 1983 170 130 90 60 50 Baccidal Kyorin 1984 75 335 340 300 250 180 180 60 50 Tomiporan Toyama 1985 100 70 60 60 60 Suncefal Yamanouchi 1985 220 110 Miocamycin Meiji 1985 60 55 50 30 20 20 Tarivid Daiichi 1985 45 390 430 420 390 350 270 140 100 Flumark Dainippon 1985 25 230 230 170 120 100 50 20 Ricamycin Toyo-jyozo 1986 20 20 30 Doyle Tanabe 1987 50 50 30 20 Cefspan Fujisawa 1987 40 300 340 360 330 170 110 70 150 Tomiron Toyama 1987 200 180 230 250 170 100 70 80 Cosmosin Lederle(JP) 1987 150 190 230 220 150 110 Meicelin Meiji 1987 80 150 170 170 120 80 70 50 Flumarin Shionogi 1988 100 380 440 480 440 260 230 220 Banan Sankyo 1989 170 290 270 190 140 200 Bareon Hokuriku 1990 70 35 80 Habekacin Meiji 1990 70 90 90 90 100 Cefzon Fujisawa 1991 170 240 300 290 Megalocin Kyorin 1993 50 60 Spara Dainippon 1993 40 80 70 Carbenin Sankyo 1993 75 110 Cravid Daiichi 1993 330 420 Meiact Meiji 1994 50 150

Source: JYakuji Handbook (Handbook of Drugs) 1986^-1996, Yakugyojihousya . (in apanese) 14 T. Hara both natural and semisynthetic antibiotics. But the extension was in the same family of drugs: Meiji's CTT was in the aminoglycoside family and Yamanouchi's was in the macrolide family. Also, no company has developed both antibiotics and quinolone-line synthetic antibacterial drugs. That is to say, if two trajectories are common in either their process technologies (for example, those of semisynthetic penicillins and cephalosporins) or their product technologies (for example, those of natural aminoglycosides and semisynthetic aminoglycosides), a CTT can easily extend over different trajectories. We may be able to say that there are several different dimensions of technological trajectories: at least, process technological trajectories and product technological trajectories.

IV. Conclusion

The findings of this study are the following. 1) We can identify the same industrial technological trajectories in Japan as those found by Achilladelis (1993) though there was a time lag in their establishment. 2) Industrial technological trajectories seem to be transferable beyond national boundaries. We can say that the Japanese case is an example of this type of transfer. 3) There may be several different dimensions of technological trajectories: at least, process technological trajectories (for example, that of natural products or synthetics) and product technological trajectories (for example, that of aminoglycosides or cephalosporins). 4) There may be a hierarchy of technological trajectories: major technological trajectories are like those of sulphonamides, antibiotics and quinolones; minor technological trajectories are like those of for injection and cephems for oral use. 5) The factors which seem to be related to the establishment of technological trajectories are a company's routine for searching, technological limits and technological opportunities, production economies and the market demands. 6) There are an only a small number of companies in a certain technological trajectory (Figure 3). This implies that there may be barriers of entry to a technological trajectory. Industrial Technological Trajectories and Corporate Technology Traditions 15

7) We can observe corporate technology traditions in the development of antibacterial drugs in Japan. Most drugs developed by each company are concentrated in a specific category. 8) Each corporate technology tradition is likely to belong to either a process technological trajectory or a product technological trajectory. This implies that there may be barriers to mobility between different technology traditions. 9) The factors which seem to be related to the emergence of corporate technology traditions in the Japanese antibacterial drug sector are licensing, research collaboration and the accumulation of complementary assets rather than the commercial success of radical innovations. 10) The factors which preserve an existing corporate technology tradition may be organizational routines, resource scarcity and resource specificity, corporate behavior based on risk aversion, the existence of specific complementary assets, institutional factors and/or past commercial successes. These factors may also be related to the mobility barriers of technology traditions.

The study of industrial technological trajectories and corporate technology traditions is useful for a better understanding of industrial technological change. It may disclose hidden, specific combinations in the existing "general" theories on technological change'. It is also useful for a better understanding of the formation of core competencies or capabilities. Both of these concepts, used mainly in the resource- based approach'. We can regard these concepts as a stock of firm- specific ability or knowledge, and a corporate technology tradition as a stream of such ability or knowledge. The better we comprehend industrial technological trajectories and corporate technology traditions, the better we understand the mechanism of technological change and technological capability formation, that in turn may result in the better management of technology. Industrial technological trajectories and corporate technology traditions seem to be more complex phenomena than Achilladelis (1993)

7. For example, Abernathy and Utterback (1978). 8. Wernerfelt (1984); Dierickx and Cool (1989); Barney (1991); Mahoney and Pandian (1992);( Amit and Shoemaker (1993); Hamel and Prahalad (1994); Leonard-Barton 1995). 16 T. Hara

described. It seems highly probable that there are many dimensions of these and many factors related to their formation. In this study, we have tried to clarify these, but this is insufficient because we did not analyze them using "substantial evidence," but using only "circumstantial evidence ." The findings should be verified by deeper case studies and comparative studies among different situations.

Received September 9, 1996.

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