GCLE's Bright Prospect    

By Wu Huifang and Lei Guangyu

GCLE (7-phenylacetamide-3-chloromethyl-3-cepham-4-carboxylic acid p-methoxybenzyl ester) as an important intermediate of cephalosporin antibiotics is not new in China. GCLE, 7-ADCA (7-aminodeacetoxyl) and 7-ACA (7-aminocephalosporanic acid) are called three major cephalosporin antibiotic intermediates. Comparatively speaking, the start of the GCLE production was not as early as 7-ADCA and 7-ACA and the production scale was also not that large. The main reason was either that CGLE downstream cephalosporin drugs were still in the patent protection period or that the use of earlier and more matured intermediates restricted the application dissemination of GCLE.
    Things have however changed in the recent two years. Both the production and the sales of GCLE have grown rapidly. According to reports made by Beijing Orientbit Technology Co., Ltd. (www.healthoo.com), the six companies in China including Tianjin Cenway Technologies Ltd., Tianjin Gencom Pharmaceutical Co., Ltd., Zhejiang Ningbo Renjian Pharmaceutical Co., Ltd., Heze Ruiying Pharmaceutical Group, Jiangsu Haici Biological Pharmacy Co., Ltd. and Changzhou Kony Pharma Co., Ltd. have already started the production and sales of GCLE. Another 3 or 4 companies are constructing production units or making trial production. Foreign GCLE producers mainly include Otsuka Chemical of Japan and the joint venture it has set up in India. The total capacity of to make GCLE in the world has reached 2 thousand t/a, and in China the production capacity is 1.5 thousand t/a. The output of GCLE in China was only 70 tons in 2004, but reached 480 tons in 2006 and 260 tons in the first half of 2007. The average annual growth was 162% from 2004 to 2006.
   There are two reasons for the rapid growth of GCLE in the past two years. One is that China has low-priced penicillin G potassium salt. The other is that due to the expiry of the patent protection period for GCLE downstream drugs such as cefixime, cefprozil, cefdinir and cefpodoxime, these drugs have been produced in India and China and the demand for GCLE is driven. Cefixime is the variety of oral cephalosporin drugs with the most rapid growth. The consumption of GCLE in cefixime production accounts for 90% of the total, and the proportion is still increasing.
   According to the survey, 90% of GCLE produced in China is for export. It is mainly sold to some cefixime producers in India such as Orchid Chemicals and Aurobindo Pharma. Small amounts are also sold to Japan and Korea. The consumption in the domestic market only accounts for around 10%.
   The export price of GCLE has increased constantly since 2006 and has already reached US$130/kg today. Such trend will still last in future. The price rise of penicillin G potassium salt in 2007 has produced some impact on the capacity expansion of GCLE, but cefixime production still has high profit and downstream producers are active in buying GCLE.
   Oral cephalosporin formulations have always been in an inferior position in cephalosporin drugs. According to the sampling survey, the market share of oral cephalosporin formulations only accounts for 13.5% in the entire cephalosporin drug market. When the first-generation and the second-generation cephalosporin drugs such as cefalexin, cefradine, cefadroxil and cefaclor enter the stage of low profit, only cefixime is an oral cephalosporin drug with relatively high profit and its clinic consumption presents a rising trend.
   Imitated cefixime imported in China is mainly from Orchid of India and Hanmi Pharm Co., Ltd. of Korea. Compared with domestic product, formulation producers prefer to purchase imports. Besides stable quality, the price of imports is not higher than that of domestic product either. The import price is equivalent to RMB4 000/kg, almost equal to the price of domestic product. The imported amount of cefixime was 5 tons in 2006 and the domestic output was around 3 tons.
   There are many cephalosporin drugs using GCLE as precursor, but varieties with matured commercialization and process route are mainly the third-generation oral cephalosporin drugs such as cefixime, cefdinir and cefpodoxime proxetil. Oral formulations have not yet developed themselves into "star" varieties like ceftriaxone. Whether cefixime can play this role is up to its application dissemination in clinics and the downturn of its retail sale price. It can be seen that after the price of cefixime becomes low, the growth of demand for GCLE will be further promoted.