The 2015 ginkgo biloba incident triggered a plant explosion
In May 2015, the CFDA organized the Food and Drug Administration to conduct a flight inspection and found that many provincial enterprises had changed the production process of Ginkgo biloba extract without authorization. The "Ginkgo biloba incident" caused an uproar in the industry, constantly implicating new downstream pharmaceutical and health product companies. The State Food and Drug Administration (hereinafter referred to as CFDA) launched a special project governance action for Ginkgo biloba drugs and health food, aiming to thoroughly purify the Ginkgo biloba drug market, severely crack down on various violations and violations, and maintain the safety of public medication. This article attempts to sort out, summarize and analyze this incident, so as to provoke thinking and warn the industry to strictly abide by laws and regulations, and use honest production and operation to ensure the safety and effectiveness of drugs and health food.
Ginkgo biloba event
1.1 Causes
From May 8 to 10, 2015, the CFDA organized the Hunan Provincial Food and Drug Administration to conduct a flight inspection of Wan Bond (Hunan) Natural Medicine Co., Ltd., and found that there were problems such as illegal purchase of ginkgo biloba extract and feeding to produce ginkgo biloba tablets and ginkgo biloba capsules, chaotic production management, and falsification of materials purchase ledger and batch production records and batch inspection records of ginkgo biloba extract.
From May 9 to 11, 2015, the CFDA organized the Guangxi Autonomous Region Food and Drug Administration to conduct a flight inspection of Guilin Xingda Pharmaceutical Co., Ltd., and found that the extraction process of Ginkgo biloba extract was changed without authorization, from dilute alcohol extraction to 3% hydrochloric acid extraction; Ginkgo biloba extract was illegally purchased from unqualified enterprises, and its extraction process was also 3% hydrochloric acid extraction; illegal Ginkgo biloba extract was used in the production and sale of Ginkgo biloba slices; the purchased Ginkgo biloba extract was re-labeled by the factory and sold to other drug manufacturers; batch production and material management records were falsified. "Ginkgo biloba incident" violations and violations.
1.2 Governance actions
The CFDA combined various means to set off a thorough investigation storm across the country for the safety risks of "problematic" ginkgo biloba extract, and local food and drug administrations began to seize and remove a series of products containing ginkgo biloba extract from problematic companies. Judging from the CFDA's determination to enforce the law, the ginkgo biloba drug and health food market will experience a wide range of shocks.
From May 19, 2015 to November 5, 2015, CFDA issued 37 documents on the governance of the "Ginkgo Biloba" special project in the form of notices, notices and announcements, and 4 announcements were issued on June 8 alone. The main governance information is as follows (data and information are sourced from CFDA).
1.2.1 carry out Ginkgo biloba medicine/health food special project governance action
On May 19, CFDA issued the "Notice on the Illegal Production and Sales of Ginkgo Biloba Drugs by Guilin Xingda Pharmaceutical Co., Ltd.". On May 20, it issued a notice on the governance of Ginkgo Biloba Drugs special project to conduct a comprehensive inspection of all Ginkgo Biloba Extract and Ginkgo Biloba Preparation manufacturers, focusing on illegal acts such as changing the extraction process without authorization, illegally adding related substances, and purchasing Ginkgo Biloba Extract from unqualified enterprises. On May 21, a video conference was held to further deploy the governance of Ginkgo Biloba Drugs special project. Emphasize the need to investigate the clues of existing cases to the end, and check the 24 drug manufacturers that purchased illegal ginkgo biloba extract from Guilin Xingda Pharmaceutical Co., Ltd. one by one. Once any problems are found, they will immediately take measures such as suspending sales and use, checking the flow, recalling products, and suspending production, and severely punish enterprises for illegal activities according to law. It is required to fully understand the seriousness of the current ginkgo biloba drug problem, take effective measures to control it, thoroughly purify the ginkgo biloba drug market, severely crack down on various violations of laws and regulations, and maintain public drug safety.
On May 25, the Supreme People's Court, the Supreme People's Procuratorate, the Ministry of Public Security, and the Ministry of Supervision were notified of the investigation and punishment of cases of illegal production and sales of ginkgo biloba drugs by Guilin Xingda Pharmaceutical Co., Ltd. and other enterprises. On May 29, the flight inspection found that Ningbo Lihua Pharmaceutical Co., Ltd. purchased some batches of ginkgo biloba extract from unqualified enterprises and sold it to other drug manufacturers in the name of the enterprise. Its behavior was suspected of violating the law. On June 4, the supplementary inspection method for free quercetin, kaempferin, and isorhamnetin in ginkgo biloba extract, ginkgo biloba tablets, and ginkgo biloba capsules was promulgated to deal with the illegal links in the production of
On June 8, ① According to the supplementary inspection method, illegal acts such as changing the extraction process and illegal addition in the production process of ginkgo biloba drugs will be detected; ② All ginkgo biloba extract manufacturers (including those who have not obtained a drug production license)extractProduction enterprises) and ginkgo biloba pharmaceutical preparation manufacturers shall, according to the supplementary inspection standards, conduct self-inspection in batches of all ginkgo biloba extract, ginkgo biloba tablets and ginkgo biloba capsules produced by their enterprises since January 1, 2014; ③ All enterprises that use ginkgo biloba extract to produce health food shall immediately conduct self-inspection according to the registered and declared production process and Quality Standards of ginkgo biloba extract.
On June 10, law enforcement inspections were carried out on enterprises that use Ginkgo biloba extract to produce health food. On August 10, Ginkgo biloba soft capsules, drop pills, Shuxuening injection and its Ginkgo biloba extract injection, Ginkgo damo injection, free quercetin in Ginkgo biloba leaf drops, kaempferol, isorhamnetin supplementary test methods and Ginkgo biloba extract, Ginkgo biloba tablets and Ginkgo biloba capsules supplementary test methods for sophoroside check items.
On September 10, the third stage of Ginkgo biloba drug special project supervision and sampling was carried out. It aims to provide technical support for the follow-up investigation and handling of Ginkgo biloba drug cases.
1.2.2 Ginkgo biloba drug special project supervision self-inspection and sampling
On June 22, 90 ginkgo biloba extract, ginkgo biloba tablets (including dispersed tablets) and ginkgo biloba capsule manufacturers conducted self-inspection in a total of 5,161 batches, with 2,335 batches of unqualified products, accounting for 45% of all batches; 55 enterprises (61.1%) of unqualified products, including 30 enterprises (33.3%) of all batches of unqualified products, including 25 enterprises (27.8%) of some batches of unqualified products.
On July 2, 284 batches were sampled in the first batch, of which 67 batches of substandard drugs were detected, accounting for 23.6% of all products, involving 24 drug manufacturers.
On July 31, 118 batches (60.8%) of unqualified drugs were detected in 194 batches of drugs sampled in the second batch, involving 31 drug manufacturers. 102 batches of drugs from 29 companies failed the self-inspection, and the sampling results were consistent with the self-inspection results of the enterprises. 16 batches of drugs from 4 companies passed the self-inspection, and the supervision sampling results failed. After in-depth investigation, it was confirmed that Heilongjiang Tianhong Pharmaceutical joint stock company, Jilin Kuahai Biochemical Pharmaceutical Manufacturing Co., Ltd., and Ningbo Lihua Pharmaceutical Co., Ltd. had illegal acts of changing samples and forging evidence and evading supervision.
On September 8, it was found that the joint stock company of Hubei Noon Pharmaceutical Industry reported false self-test results, and at the same time falsified batch production inspection records and exchanged sample samples, which caused the CFDA to include the company in the "Notice on Self-Inspection of 90 Ginkgo Biloba Extract and Ginkgo Biloba Drug Production Enterprises" (No. 24, 2015).
On October 15, a total of 168 batches of samples were inspected, including 38 batches of Ginkgo Biloba Soft Capsules, 24 batches of Ginkgo Biloba Dropping Pills, 62 batches of Shuxuening Injection, 7 batches of Ginkgo Biloba Extract Injection, 36 batches of Ginkgo Biloba Injection, and 1 batch of Ginkgo Biloba Drops. Among them, 16 batches of unqualified Ginkgo Biloba Soft Capsules were detected, and 3 unqualified drug production enterprises were found; 13 batches of unqualified Ginkgo Biloba Dropping Pills were found, and 1 unqualified drug production enterprise was found. No unqualified products were found in 4 varieties of Shuxuening Injection, Ginkgo Biloba Extract Injection, Ginkgo Biloba Damo Injection, and Ginkgo Biloba Drops.
On October 15, among the 185 batches of unqualified ginkgo biloba drugs detected in the first and second stages, a total of 125 batches of sophoroside were detected, involving 27 companies suspected of illegally adding or using illegally added ginkgo biloba extracts for the production of ginkgo biloba drugs.
The unqualified rate of self-inspection was 45%. Based on the supervision and sampling of the two-stage Ginkgo Biloba drug special project, the coverage rate of sampling enterprises reached 78%, the coverage rate of product batches reached 12%, and the unqualified rate of sampling inspection was 38.7%. The sampling results showed that the self-inspection results of the vast majority of drug manufacturers were credible. The unqualified drugs involved 57 drug manufacturers, accounting for 62% of all the inspected enterprises. The unqualified Ginkgo Biloba drug had a detection rate of 67.6%, involving 27 enterprises. The unqualified rate of Ginkgo Biloba soft capsules was 42.1%, and the unqualified rate of Ginkgo Biloba Drop Pills was 54.2%; 3 injections such as Shuxuening injection did not detect unqualified products.
1.2.3 special project to monitor health food
The CFDA issued a notice on the self-inspection of health food, etc. On July 3, a total of 168 companies using ginkgo biloba extract to produce health food submitted their self-inspection status. Among them, 157 companies used ginkgo biloba extract to produce health food, and self-inspected 359 batches of ginkgo biloba extract raw materials. Among them, 328 batches were qualified, 13 batches were unqualified, and 18 batches were still under inspection. 8 health food companies were involved in unqualified ginkgo biloba extract raw materials. On July 7, 203 companies using ginkgo biloba extract to produce health food were investigated, of which 129 companies in production purchased and used unqualified ginkgo biloba extract raw materials. The inspection found that 5.94 tons of suspected unqualified raw materials and 30.864 tons of unqualified health food were suspected.
1.2.4 Ginkgo Biloba Extract Product Test Results
The specific results are shown in Tables 1 to 4. The self-inspection information of Ginkgo biloba extract products shows that all batches of products of 7 companies failed 53 batches; some batches of products of 8 companies failed 77 batches and qualified 225 batches; all batches of products of 20 companies qualified 959 batches; a total of 1314 batches, a total of 130 batches of unqualified batches, 1184 batches of qualified batches, 9.89% of unqualified batches, 20.00% of all batches of unqualified products, 22.85% of some batches of unqualified products, and 42.85% of unqualified products.
At present, there are 118 domestic drug approvals for ginkgo biloba oral preparations, and nearly half of the companies are involved. There are 11 listed companies involved, affecting 247 health product companies. The ginkgo biloba preparation market with a scale of about 4.50 billion yuan is affected. At the same time, the flow of problem drugs (health food) is complicated. More than 20,000 hospitals in 26 provinces and cities across the country have been affected. There are also difficult-to-check health food sales end points. It is not easy to recall them all.
1.3 Punishment
On November 5, 2015, the CFDA issued the "Notice on Penalties for the Illegal Production and Sales of Ginkgo Biloba Extracts and Preparations" (No. 219, 2015), which proposed a classification of penalties for the illegal production and sale of Ginkgo Biloba Extracts and Preparations, as shown in Figures 3 to 5 (information sourced from the CFDA).
Analysis and Thinking of Ginkgo Biloba Event
2.1 Applications and Markets
2.1.1 ginkgo biloba preparation
The modern development and application of ginkgo biloba began in Germany, mainly acting on blood circulation disorders such as the brain and periphery, and has good curative effect on dementia, vascular dementia, and senile dementia. Ginkgo biloba extract preparations and health foods can be described as one of the most popular plant medicine products on the world market today. Since the 1960s, foreign scientists took the lead in extracting ginkgo flavonoids and ginkgo terpene lactones, which are anti-cardiovascular and cerebrovascular diseases, from the leaves of ancient Chinese tree species - ginkgo biloba, various ginkgo preparations around the world, as well as various ginkgo health foods and cosmetics containing ginkgo biloba extract, have filled the market. Ginkgo biloba extract preparations are sold in at least more than 130 countries around the world, including the United States, Western Europe and Northern Europe, which have a high incidence of cardiovascular diseases. In 2013, the global sales of ginkgo biloba preparations reached 7 billion US dollars. In our country's hospital prescription and retail drug markets, ginkgo biloba preparations play an important role in the combination of cardiovascular diseases and neurological diseases. They are listed in the 2009 National Medical Insurance List, the National Essential Drug List (2012) (Ginkgo biloba capsules, tablets, drop pills), and the Low Price Drug List (Ginkgo biloba tablets, capsules).
Since the 1990s, ginkgo biloba extract preparation has been the first choice for the treatment of cerebrovascular diseases. The annual sales of ginkgo biloba extract preparation in our country have developed from 600 million in 2000 to 2.20 billion in 2007. In 2011, it is estimated that it exceeded 5 billion and became one of the leading varieties of plant drugs in the field of cardiovascular and cerebrovascular. According to the "Rule of Law Weekend" report in 2015, industry data shows that in 2013, the domestic hospital cerebrovascular and anti-dementia drug market has reached 22.50 billion yuan, of which the ginkgo biloba preparation market accounted for 20%, about 4.50 billion yuan. In addition, the sales market of ginkgo biloba extract has reached 1 billion yuan, which is a "blockbuster" super variety of traditional Chinese medicine. Taking effective measures to control this variety and thoroughly purify the market will have an exemplary effect on the traditional Chinese medicine industry.
2.1.2 Ginkgo Biloba Extract
China is the world's largest producer of ginkgo biloba extract, with industry capacity accounting for more than 50% of the world's total capacity. In 2013, China's ginkgo biloba extract output reached 348.6 tons, accounting for 48.5% of the world's total output in the same period (Figure 6). By 2014, global ginkgo extract production reached 888.8 tons.
There are more than 100 domestic ginkgo biloba extract processing enterprises, but the ginkgo biloba processing industry is highly fragmented, and due to insufficient domestic demand, most of our country's ginkgo biloba extract production can only be used for export, data show that in previous years, our country's ginkgo biloba extract exports accounted for about 80% of the total output of domestic ginkgo biloba extract. Domestic ginkgo biloba extract enterprises are mostly reduced to primary raw material suppliers, at the bottom of the industrial chain, and have low bargaining power in the international market.
Ginkgo Biloba ExtractIt is a variety with huge market demand and relatively stable supply, but the specifications of Ginkgo biloba extract in our country and international demand have not yet been in line, and there are not many Ginkgo biloba extract in line with export grade. This is in sharp contrast to the rapid growth of Ginkgo biloba extract exports in Japan and South Korea in recent years, and the quality is generally better than that of our country's products. But at the same time, it brings opportunities to enterprises that supply Ginkgo biloba extract to the high-end market route. This industry rectification lays the foundation for the Ginkgo biloba extract enterprises in our country to produce high-quality products in the future, so that the Ginkgo biloba extract industry will usher in a period of rapid growth.
2.2 Reasons for the "Ginkgo Biloba Incident"
2.2.1 Quality Standards are Imperfect
Flavonoids and terpene lactones are active ingredients in Ginkgo biloba extract, and Ginkgo biloba acids are toxic ingredients. The main indicators under the Chinese Pharmacopoeia are listed in Table 5.
Determination of the amount of total flavonol glycosides using methanol-25% hydrochloric acid solution (4:1) was heated and refluxed for 30 min, the flavonol glycosides were hydrolyzed into glycosides (FIG. 7), plus the original free three glycosides to calculate the total amount.
Total flavonol glycosides = (quercetin, kaempferol, isorhamnetin) × 2.51. In 1993, Stichet first proposed the conversion factor quercetin (2.51), kaempferol (2.64), isorhamnetin (2.39) concept to calculate the amount of total flavonol glycosides, the above conversion factor is based on the Ginkgo biloba flavonoids that the most active cinnamyl flavonoid glycosides (cinnamoylflavonolglycosides) of the average relative molecular weight of 760 and the relative molecular weight of the glycoside converted from; "United States Pharmacopoeia" to the conversion factor quercetin (2.504), kaempferol (2.588), isorhamnetin (2.437) or the average conversion factor 2.51 to calculate the amount of total flavonol glycosides, these conversion factors are converted to the average relative molecular weight of flavonol glycosides 756.7, Ginkgo biloba and its preparation flavonoids The amount of domestic and foreign standards have generally used this coefficient calculation. However, this detection method is not enough to play a role in identifying fakes and distinguishing fakes, which brings opportunities to change the process and add illegal substances. Terpene lactone compounds are characteristic components of Ginkgo biloba, which are rare natural compounds. So far, they have not been found in other plants, and there is no problem of illegal addition. The industry standard has been in a vacuum for a long time, and the national pharmacopoeia ginkgo leaf extraction standard process has not been implemented by the production enterprises for a long time, resulting in a long-term chaotic and disorderly state of the entire industry. However, due to the rigid demand products of plant extracts, the world's major economies have very strong demand for them, resulting in a growing market size that masks the negative impact of the lack of standards on the industry. In response to the Ginkgo biloba extract incident, the CFDA issued two supplementary inspection methods (Table 5) to monitor the widespread problem of process changes and illegal additions in the industry. The CFDA said that unauthorized changes to the extraction process have the risk of "decomposing the active ingredients of the drug and affecting the efficacy of the drug", but due to the lack of clinical data, it is currently unclear what specific harm will be caused. The health hazards of Ginkgo biloba extract pharmaceuticals (health foods) produced by hydrochloric acid instead of ethanol need to be further studied.
2.2.2 the temptation of profiteering
The current standard of ginkgo biloba extract in our country cannot detect "changes in the process", and most people in the industry are secretive about how much cost can be saved by switching to hydrochloric acid extraction. Some media have publicly pointed out that if you switch to 3% hydrochloric acid extraction, you can save 4,000 yuan per ton; it can not only reduce costs, but also improve yield. It takes about 1 week to produce 1 ton of ginkgo biloba extract with dilute ethanol, and the output is only a few tons a year. Switching to hydrochloric acid extraction can shorten the basic process time. In addition, from this sales path alone, the profits of ginkgo biloba extract produced by unqualified enterprises can be seen after 3 "reselling" of enterprises of a certain scale. In addition, if the product itself is not up to standard, it can also be made up by other chemical means. At present, there are still some bad companies on the market whose ginkgo biloba leaf extracts rely on adding flavonoid extracts such as rutin and quercetin, or even completely blending with rutin to achieve the standard of 24% total flavonol glycosides. The added substances mainly include the dried flower buds and mature fruit extracts of the leguminous plant Sophora japonica L., the former is called locust rice, the latter is called locust horn, or the isolated and purified rutin and quercetin are extracted from locust rice. One of the 2015 editions of the Chinese Pharmacopoeia stipulates that locust rice contains no less than 20.0% of total flavonoids; locust rice contains no less than 15.0% of rutin. Sophora sinensis contains not less than 4.0% of sophorin (isoflavones), and their extraction process is simple and low-cost. Query Alibaba.com, Sophora sinensis extract is 80-100 yuan/kg, containing 95% rutin 240-300 yuan/kg, containing 98% rutin 500-550 yuan/kg, containing 98% quercetin 400-550 yuan/kg; Sophora sinensis extract (quercetin-rutin 10:1) 140 yuan/kg; Sophora sinensis extract is 60-85 yuan/kg, which shows the low and simple cost of illegal addition or blending. Unscrupulous traders use the illegal addition of the above cheap substances to make huge profits. Due to the lack of honesty and the temptation of profiteering, business operators dare to take risks and change the production process and illegal addition of Ginkgo biloba extract without authorization.
2.2.3 lack of effective supervision
The Ginkgo biloba extract incident further highlights the need to strengthen the supervision of extract production. Illegal extraction of Ginkgo biloba extract has been a problem for a long time, not just in the past two years, and the problem is not only Ginkgo biloba extract. Compared with drugs, our country's supervision of health food is even weaker. There is no review of the production process of raw materials, and there is no unified implementation of Quality Standards. CFDA began to require health food production to comply with GMP standards in 2014, but in fact there is no GMP certification for health food manufacturers, and there is no corresponding review. There is a regulatory vacuum.
The cultivation, harvesting, processing, storage, market circulation of medicinal materials, plant extraction, and production of pharmaceutical companies will all affect the effective play of the efficacy of Ginkgo biloba leaves, and the production quality assurance of each link is required. In the current supervision system of the traditional Chinese medicine industry, the Ministry of Agriculture, CFDA, the Health and Family Planning Commission, the State Administration for Industry and Commerce, and the Ministry of Public Security all have certain responsibilities in the supervision process of the traditional Chinese medicine market, and when necessary, the supervision method of joint law enforcement is adopted. The supervision standards of different departments also involve the issue of decoupling of various links. This kind of supervision itself is unreasonable. At present, there is a problem of "water control in Kowloon" in the processing, production, and sales of traditional Chinese medicine. Supervision should be full and consistent, rather than hard or surprise.
This time, the regulatory authorities focused on rectifying ginkgo biloba extract and its preparations, and the impact on the market may be a "milestone", which may raise the entry threshold of this industry in the short term.
2.3 How to prevent such incidents from happening
2.3.1 strengthen supervision
Extracts and extracts of traditional Chinese medicine are the prerequisite and material basis for ensuring the controllable, safe and effective quality of traditional Chinese medicine. In recent years, with the large-scale and intensive development of traditional Chinese medicine production, the problems existing in the process of extracting or purchasing traditional Chinese medicine extracts are more prominent, which brings hidden dangers to the quality and safety of traditional Chinese medicine. In order to strengthen the supervision and management of traditional Chinese medicine extracts and extracts, standardize the production behavior of traditional Chinese medicine, and ensure the quality, safety and effectiveness of traditional Chinese medicine, CFDA issued the "Notice on Strengthening the Supervision and Administration of Extracts and Extracts in the Production of Traditional Chinese Medicine" on July 29, 2014. It implements the filing management of traditional Chinese medicine extracts of separate national drug standards. For traditional Chinese medicine extracts that do not belong to the filing management, they should Mandatory requirements From January 1, 2016, all proprietary Chinese medicine manufacturers that do not have the ability to extract traditional Chinese medicine will stop the production of corresponding varieties, which will greatly change the current regulatory loopholes in plant extracts.
The "ginkgo biloba incident" is just one of the events in plant extracts, which has led to further regulation and supervision of the plant extract market by the state, which will make the plant extract market more efficient and standardized.
The CFDA requires all enterprises that use Ginkgo biloba extract to produce health food to conduct self-inspection, including: (1) whether to purchase Ginkgo biloba extract from the above enterprises and use the raw materials to produce finished products and sales; (2) whether to use hydrochloric acid process Ginkgo biloba extract to produce health food; (3) whether to use Ginkgo biloba and its extract in violation of approved processes and formulas; (4) whether to illegally add other substances to the raw materials of Ginkgo biloba extract used; (5) whether to produce products containing Ginkgo biloba and its extract without obtaining a health food approval number. It is worth noting that the CFDA for the first time issued "Ginkgo biloba extract used in the production of health food must be consistent with the production process and Quality Standards of Ginkgo biloba extract declared in the health food registration". It is imperative to strengthen the supervision of health foods.
2.3.2 integrity management
The "ginkgo leaf incident" fully exposed the lack of integrity of enterprises. In the modern market economy era of economic globalization, with the development of informatization and the rise of the network economy, integrity has become a passport for enterprises to expand exchanges, promote cooperation, and go global. The benefits brought by integrity and the damage caused by dishonesty will be multiplied by economic globalization.
2.3.3 develop rigorous Quality Standards
In response to the irregularities in the production of Ginkgo biloba extract, the CFDA issued two supplementary inspection methods, but they are not the most effective methods. The best way to solve the problem of fraud is to establish a control/characteristic/spectral effect fingerprint of total flavonoids in Ginkgo biloba leaves, which belongs to the chemical components of 8 cinnamyl flavonoids and proanthocyanidins characteristic peaks, semi-quantitatively stipulates the area and ratio of quercetin, kaempferol, isorhamnetin peaks, and the similarity shall not be less than 0.90, and formulate rigorous and meticulous Quality Standards for extracts and their preparations to strictly control the quality and prevent counterfeiting.
2.3.4 raise standards
Ginkgo biloba and its preparations are internationally implemented according to European and American standards. German and French companies have become the benchmark and leader of the industry, and they set the rules of the game. By raising the threshold and raising the standard, other companies can be restricted from entering and weaken the advantages of opponents. The quality control standards for Ginkgo biloba extract and its capsules and tablets included in the 2015 USP38 edition of the United States Pharmacopoeia are the highest standards currently being implemented. Since the 21st century, the research on innovative drugs of ginkgo biloba in our country has made great progress and achieved significant results, not lagging behind Germany and France and surpassing their innovation. In terms of standard formulation, our country should make a difference and innovate, including GLP planting standards, GMP standards for each production link and their Quality Standards and a series of standardized controls, forming technical barriers in this industry. We must spare no effort to develop standards higher than those in Europe and the United States, and it absolutely has the voice over in the world, and formulates the rules of the game.
2.3.5 Brand Strategy
According to statistics, from 2005 to 2006, imported ginkgo biloba preparations held a major share in the domestic market, especially in the field of injections, with sales leading the way. From 2007 to 2014, domestic enterprises stepped up their development efforts, gradually reversing the situation of foreign companies dominating the market, and domestic preparations dominated the market. According to the data of sample hospitals in 22 cities in China, in 2014, there were more than 50 ginkgo biloba preparation manufacturers, and the top 10 companies accounted for 91.4% of sales. Among them, the top 4 companies are Dr. Weimashupei Pharmaceutical Factory (Germany), with sales of 132 million yuan; Heilongjiang Zhenbao Island Pharmaceutical, with sales of 129 million yuan; Hebei Shijiazhuang Shenwei Pharmaceutical, with sales of 97.40 million yuan; Beijing Shuanghe Pharmaceutical, with sales of 73.01 million yuan, market share was 16.9%, 16.6%, 12.5%, 10.4% respectively. The ginkgo biloba preparation of Dr. Weimashupei Pharmaceutical Factory in Germany grew by 27.1% in 2014 compared with the same period, while the product sales of four domestic companies decreased compared with last year. Dr. Weimar Shupei pharmaceutical factory production of Jinnado (120 tablets/bottle, 40mg/tablet) priced at 450 yuan/bottle, and Kangbei pharmaceutical production of Tianbaoning (84 tablets/bottle, 40mg/tablet), priced at 53 yuan/bottle, 2 unit price difference of 5.95 times; Taiwan Jisheng chemical pharmaceutical factory joint stock company production of Jinnado injection (17.5mg/piece) priced at 22 yuan/piece, while Heilongjiang Zhenbao Island pharmaceutical joint stock company production of Shuxuening injection (17.5mg/piece) priced at 5.5 yuan/piece, two price difference of 4.07 times, if it is Dr. Weimar Shupei pharmaceutical factory production price difference is also more than 5 times, which fully reflects the core competitiveness of the brand value. In addition, it is worth mentioning that Ginkgo biloba preparations ranked 11th, 21st, 23rd, and 32nd among the top 100 drugs in the sample hospitals from 2011 to 2014, respectively, with the ranking decreasing year by year. After more than 10 years of development, there are many domestic enterprises of Ginkgo biloba preparations, and the competition is fierce, and the price reduction has become inevitable.
This industry rectification is likely to achieve industry reshuffle and increase enterprise concentration. The government must take action to strengthen quality management, guide the construction of industrial brands, and form a competitive situation with foreign brands such as Germany and France. Use the sharp tools of brand strategy to gain a competitive advantage and gradually develop and grow, so as to ensure the long-term development of the industry.
2.3.6 claims, accountability and penalties
Judging from the current punishment opinions issued by the CFDA, if it can be implemented without compromise, it will have a certain deterrent effect on enterprises, reflecting the huge cost of violations. The illegal production and sale of ginkgo biloba extract and preparations will be punished according to the severity of the circumstances. The illegally produced and sold products and illegal income will be confiscated, and a fine will be imposed, the "Drug Production License" will be revoked, the approval certificate of ginkgo biloba drug will be revoked, and the legal representative of the enterprise, the person in charge of the enterprise, the person in charge of quality, the person in charge of production and other relevant personnel who are directly responsible for the crime will be transferred to the public security organ for criminal responsibility according to law. The ginkgo biloba incident did great harm to traditional Chinese medicine enterprises, and the impact on traditional Chinese medicine enterprises was no less than that of the poison capsule incident. If the source enterprises were not punished severely, traditional Chinese medicine enterprises would also suffer.
The "ginkgo biloba incident" has made people soberly aware that only by establishing a set of effective claims, accountability and punishment mechanisms from a legal perspective can we effectively reduce the occurrence of such incidents.
3 Conclusion
3.1 Product quality
Product quality does not depend on inspection to find problems, but should be strictly supervised, enforced law enforcement, severe penalties, severe crackdowns, and source governance. Only by being honest and law-abiding in the production and operation of enterprises can we ensure that product quality is free from problems.
3.2 Opportunities brought by the Ginkgo biloba incident
The "ginkgo biloba event" will make the market develop more rationally and standardized, and the plant extract market will not only not be compressed, but will also show a greater development momentum. Moreover, the plant extract market will usher in the favor of capital markets, which will help the quality of plant extracts improve and the market develop faster. Entrepreneurs with strategic vision will be able to gain good opportunities for development from small events.
This market has entered a period of rapid growth. With the advancement of national health goals and the high recognition of plant extract products globally, the plant extract market will usher in a higher development speed. It is believed that as the country gradually strengthens norms and guidance, plant extracts will become a high-speed and benign development industry.
