江苏华兰药用新材料股份有限公司

Abstract from: http://www.cnpharm.com/site1/zgyyb/html/2008-10/09/content_12882.htm

 　　                                               

Journalist: Wang Huafeng, Dong Xiaofei

 

Market is good and evil

 

 Blindly reduce cost

 

Supply of imported pharmaceutical raw material is in short, it is hard to contain the trend of irregular market, compatibility problem between cephalosporins preparations for injection and butyl rubber stopper emerges.... This year, butyl rubber stopper industry has frequent waves and has attracted peoples' attention. On product quality symposium of butyl rubber stopper manufacturers held by CNPPA in recent days, some insider pointed out, irregular competition in current domestic butyl rubber stopper industry was mainly shown that, to reduce cost, part butyl rubber stopper manufacturers added non-pharmaceutical butyl rubber in their "pharmaceutical butyl rubber stopper" products without sufficient experiments on compatibility test, which greatly increased hidden safety dangers of drugs for transfusion. In this case, as long as strengthening industrial self-discipline, improving R&D capability, enhancing market supervision and control, it was possible to eliminate such dangers to public drug safety.

 

Market is good and evil

 

"Cost of a butyl rubber stopper with its diameter of 20mm is RMB0.11, while some enterprises sell at 0.08~0.09 only." Mr. Hua Guoping, the president of Jiangyin Lanling Bottle Stopper Co., Ltd felt shrug and pained about disorder in current domestic butyl rubber stopper market. He said, viscious competition in current domestic butyl rubber stopper market had brought attention of related authorities, however, as the fiercer and fiercer supply of butyl rubber, weak supervision and control measures, phenomenons like add other false substances or change source of raw material and formula without submitting any application to related authorities increase.

 

As introduced, price of imported pharmaceutical butyl rubber from May to Aug this year was RMB105000/ton, dipped a little in the last third of Aug, but still remained at about RMB90000/ton. Besides, costs for production factors of rubber stoppers including water, electricity, gas, etc. increased, while sizes and weights of rubber stoppers of different specifications had their own fixed standards, in this case, yield ratio can increase 8% at most even through matrigel edges are added as well as utilization cost of such matrigel edges will increase 5%. But "why are rubber stoppers at so tall price supplied to the market? It is possible for ordinary butyl rubber stopper that price difference shall be ranged from RMB0.003~0.005, while now is RMB0.01~0.03. " Mr. Hua Guoping thought, reason for such "strange phenomenon" was simple, that was part enterprises attempted to attract customers at a lower cost by adding false substances.

 

This phenomenon doesn't only lead to fierce viscious competition which makes regulatory enterprises using real pharmaceutical raw materials suffer from heavy losses but also buries critical hidden dangers to public drug safety. Mr. Hu Changqin, the director for Antibiotics Section of National Institute for the Control of Pharmaceutical and Biological Products pointed out, neither of cleanliness, chemical stability, air tightness or biological properties is better than butyl rubber stopper, but after butyl rubber stopper is added drugs to with stronger molecular activity for packing, some extractions in the rubber stopper may be slowly released and absorbed by drug so as to produce compatibility problem between the rubber stopper and drug. The study results show that, use of injection preparations with turbidity (clarity) out of limits will cause dangers to patient's health and lift security. For butyl rubber stopper added with other ordinary rubber, there's no doubt that it will greatly enlarge hidden dangers of product quality and safety.

 

Blindly reduce cost

 

"In fact, such phenomenon in the market is an old term and reason for such phenomenon is complex"Mr. Tai Bowen, General Manager of Sheng Zou Rubber & Plastics ( Soochow ) Limited said, in addition to part enterprises are under the pressure of big bulge in price of raw materials, the facts such as drug sampling inspection is not strictly implemented, domestic pharmaceutical industry has excess capacity as well as viscious competition at low price are all key factors.

 

As we all know, due to attack by hurricane, some plants of ExxonMobil -- main supplier for international butyl rubber market stopped production, plus effect of financial rate and difficulty in booking cargo spaces, in recent months, supply of butyl rubber is in shorter and shorter, some domestic butyl rubber stopper manufacturers who have long-term stable business relationships with ExxonMobil haven't obtained sufficient supplies yet.

 

Meanwhile, sampling inspection hasn't been implemented against injection preparations in accordance with related regulations so pharmaceutical manufacturers have chances to exploit an advantage. As introduced, injection preparations shall be valid for 2 years, that is to say, during quality test and time discrimination of such injection preparations, drug liquid shall never have defective problem of turbidity (clarity) within such validity. Hua Guoping said, sometimes, it was difficult to find turbidity (clarity) out of limits during sampling inspection, because samples must be retained for the drug to be inspected as per related regulations, but now, products on the market were tested instead of the samples within certain validity retained. If product which leaves factory for a short time is tested, then rubber stopper hadn't obvious reaction with drug liquid, so all indexes might be within an normal range. Usually, injection preparations using butyl rubber stoppers are pharmaceuticals at a large amount commonly used in clinic, the vast majorities were launched into clinic use within a few weeks or months, so problems were difficult to see. Besides, some pharmaceutical manufacturers follow up circulation and use status of the drugs, if such product is not used within a long term, they would take immediate actions to call products back, so "weak point" may not be found.

 

Cai Hong, Vice chairman of CNPPA analyzed: "capacity of rubber stopper industry is excessive enough so that some manufacturers wrongly choose sacrifice product quality when it is difficult to give consideration to both quality and price". As introduced by her, so far, there are about 40 domestic rubber stopper manufacturers which have obtained registration of pharmaceutical packaging materials and sales volume of the top 17 manufacturers of rubber stoppers for powder injections was about 10200000000 pieces by 2007 according to statistics from CNPPA. Besides, according to statistics from Association of Chinese Chemical Pharmaceutical Industry, sales volume of rubber stoppers for powder injections all over China was about 10200000000 pieces by 2007. That is to say, even though limited export is counted in, total capacity of top 20 domestic manufacturers can satisfy market needs. Due to excessive industry capacity, to seek for survival, some enterprises may be unscrupulous in their efforts, ignoring product quality but competing at low prices.

 

Extreme low profit also makes manufacturers of injection preparations become sensitive to cost so non-rational selection of rubber stopper appears. Principle of a large pharmaceutical enterprise in Shandong said, as affected by vicious competition at low price as well as unscientific drug pricing system, factory price of injection preparations like cefazolin and cefalexin is usually RMB1~2/piece , ceftriaxone (250mg) is less than RMB1. All these products are of small profits, even sustain losses, so enterprises has no way to maintain production but reduce costs. Besides, many manufacturers of injection preparations attempt to take chance: assume producing 50000000 bottles of Ceclor injection preparations a year, if rubber stopper at a price of RMB0.08/piece was used, then packaging fee would be RMB4000000; if rubber stopper at a price of RMB0.15/piece was used, then packaging fee would be RMB3500000 more. Even if they were punished 10 times a year, and maximum penalty is RMB200000 each time, then RMB1500000 was still gained. In this case, they decided to rush ahead into danger.

 

Advocate industry self-discipline

 

On this product quality symposium, an authority who had worked in the field of drug registration for a long period poured out his endless grievances when facing to manufacturers of butyl rubber stoppers, he calmly asked: "today, here are all manufacturers of butyl rubber stoppers, if sitting face to face with pharmaceutical manufacturers, who dare to guarantee all batches of his rubber stoppers never have quality problems?" Several minutes' silence have all participants feel awkward. In 2006, CNPPA has ever sent an initial written proposal for honesty and self-discipline to the whole industry. On this symposium, someone proposed to build an honesty union and make honesty presentation among all manufacturers of butyl rubber stoppers for two times but there was not a much more muted response. Some insiders felt worried that, if such manufacturers has no confidence to their own product quality, how to gain foreign trust or sustainable development? Experts on this symposium expressed, as long as professional association further played an effective role, manufacturers of rubber stopper and drugs enhanced communications, high-tech innovative ability and industry concentration were improved and whole-course supervision and control were enhanced by related national authorities, it was possible to change the current passive patten.

 

"After the Sanlu Scandal, a few drug manufacturers called me to consult potential bad consequences caused by using butyl rubber stoppers with quality problems, it is thus clear that the Sanlu Scandal has positive influence on and warns against the drug manufacturing and pharmaceutical packaging industry. " Mr. Zhang Wei, the head of Shanghai Food and Drug Packaging Material Control Center said, irregular behaviours of some butyl rubber stopper manufacturers had huge harm and directly threatened public drug safety. Industry self-discipline was a guarantee for sustainable development of the industry, industrial association should fully play a role as coordination and guidance to promote the industry to improve its consciousness of self-discipline. The association could regularly calculate, fix and publish cost price of rubber stopper for the reference of drug manufacturers before their procurement and offer evidence for the supervision and control of related authorities. Besides, collect copies of original invoices for monthly procurement in order to verify if the source of rubber material belongs to pharmaceutical level and judge normalization status of corporate production in accordance with current price of rubber material. Meanwhile, association should make out standards for raw materials and auxiliary materials for butyl rubber stopper as soon as possible as well as list of auxiliary materials and assistant which can be added or not.

 

"On this matter, manufacturers of rubber stoppers and drugs shall march in the same pace and enhance communication." Cai Hong thought, drug manufacturers shall have the right to know and manufacturers of rubber stoppers shall publish formula system and ingredients added to all users in addition to product code. Besides, drug manufacturers shall also supply manufacturer of rubber stoppers the information in relation to production process of the drug in order to guarantee uniformity and stability of drug quality. In this case, know both ourselves and our adversaries, the both parties can take joint responsibilities for drug quality and safety.

 

Supervision authorities enhance the control to the whole-course production of rubber stopper, strictly implement sampling inspection and seriously punish illegal behaviours are also key measures taken to purify the market. It is known that SFDA sent a notice on chemical injection preparations on Jan 10, asking to implement sampling inspection on site, reserve samples and implement full inspection in 2 months before validity expires for data of final assessment of drug safety and effectiveness. Cai Hong hoped, in addition to enhancing market supervision and control, inspection on production process and formula should also be strengthened. "On this basis, strengthen the intensity of checking and punishment against illegal behaviours and public to the society immediately in order not let such irregular enterprise have an opportunity that can be exploited to its advantage."

 

In fact, it is the effective method to break through the current difficulty by improving technical innovation ability of butyl rubber stopper industry as well as industrial concentration. Zhang Wenfang, the CTO of Aoxing Group emphasized that, in manufacturers of rubber stoppers in some developed countries in EU and US, their labor intensity and production equipment may not be more superior than domestic manufacturers of pharmaceutical packaging materials, but they focused on "software" construction. Domestic enterprises shall strengthen research and development and take active exploit on product quality, stability and customization instead of racking their brains for cost reduction.

 

Enterprises and experts on the symposium jointly suggested related department strengthen macro guidance and raise industry access threshold in order to improve industrial concentration.