Ginkgo leaf chaos awakens the market of extracts of pharmaceutical companies

In May 2015, the "ginkgo leaf event" caused by the enterprise's unauthorized change of the production process of ginkgo leaf extract has been implicated in the new downstream pharmaceutical and health product enterprises The State Food and Drug Administration (CFDA) carried out ginkgo leaf drugs and The health food special treatment action aims to thoroughly purify the ginkgo leaf drug market, severely crack down on all kinds of illegal and illegal behaviors, and maintain the drug safety of the public This paper attempts to sort out, summarize and analyze this incident, so as to trigger thinking, to warn the industry to strictly abide by laws and regulations, and to ensure the safety and effectiveness of drugs and health food by honest production and operation Cause of ginkgo leaf event 1.1 From May 8 to 10, 2015, CFDA organized the food and Drug Administration of Hunan Province to conduct flight inspection on Wanbang (Hunan) Natural Medicine Co., Ltd and found that there were problems such as illegal purchase of Ginkgo biloba extract for feeding and production of Ginkgo biloba leaves and Ginkgo biloba capsules, disordered production management, forgery of material purchase account, batch production record and batch inspection record of Ginkgo biloba extract, etc From May 9 to 11, 2015, CFDA organized Guangxi food and drug administration to carry out flight inspection on Guilin Xingda Pharmaceutical Co., Ltd and found that it changed the extraction process without authorization to produce Ginkgo biloba extract, which was extracted by dilute alcohol Change to 3% hydrochloric acid extraction; unqualified enterprises purchase Ginkgo biloba extract illegally, and its extraction process is also 3% hydrochloric acid extraction; use illegal Ginkgo biloba extract for Ginkgo biloba leaf production and sales; replace the label of the factory and sell it to other drug manufacturers; forge batch production and material management records "Ginkgo leaf incident" illegal behavior 1.2 the CFDA comprehensive measures set off a nationwide thorough investigation storm for the safety risk of "problem" Ginkgo biloba extract, and drug regulatory bureaus around the country began to seal up and remove the related Ginkgo biloba extract series products containing problem enterprises From the perspective of CFDA's determination to enforce the law, there will be a wide range of shocks in the market of Ginkgo biloba drugs and health food From May 19, 2015 to November 5, 2015, CFDA issued 37 special governance documents related to "Ginkgo biloba" in the form of notices, notices and announcements, and issued 4 announcements on June 8 alone The main governance situation is as follows (data and information are from CFDA official website) 1.2.1 on May 19, CFDA issued the notice on illegal production and sale of ginkgo leaf drugs by Guilin Xingda Pharmaceutical Co., Ltd and other enterprises On May 20, the notice on the special treatment of Ginkgo biloba drugs was issued to conduct a comprehensive inspection on all Ginkgo biloba extract and Ginkgo biloba preparation manufacturers, focusing on the illegal activities such as changing the extraction process without authorization, illegally adding related substances, and purchasing Ginkgo biloba extract from unqualified enterprises On May 21, a teleconference was held to further deploy the special treatment of Ginkgo biloba drugs It is emphasized that the existing case clues should be checked to the end, and 24 drug manufacturers who purchase illegal Ginkgo biloba extract from Guilin Xingda Pharmaceutical Co., Ltd should be checked one by one Once problems are found, measures such as stop selling and stop using, check the flow direction, recall products and suspend production should be taken immediately, and the illegal acts of enterprises should be punished seriously according to law We need to fully understand the seriousness of the current ginkgo leaf drug problem, take effective measures to control it, thoroughly purify the ginkgo leaf drug market, severely crack down on all kinds of illegal behaviors, and maintain the public drug safety On May 25, the Ministry of public security and the Ministry of supervision informed the Supreme People's court, the Supreme People's Procuratorate, the Ministry of public security and the Ministry of supervision of the investigation and handling of cases of illegal production and sale of ginkgo leaf drugs by Guilin Xingda Pharmaceutical Co., Ltd and other enterprises On May 29, flight inspection found that Ningbo Lihua Pharmaceutical Co., Ltd purchased some batches of Ginkgo biloba extract from unqualified enterprises and sold it to other pharmaceutical manufacturers in the name of the enterprise, which was suspected of violating the law On June 4, the supplementary inspection method for free quercetin, kaempferol and isorhamnetin in Ginkgo biloba extract, Ginkgo biloba leaf and Ginkgo biloba leaf capsule was issued to deal with the illegal links in the production of Ginkgo biloba extract On June 8, ① according to the supplementary inspection method, illegal activities such as changing the extraction process and illegal addition will be detected in the production process of Ginkgo biloba drugs; ② according to the supplementary inspection standard, each Ginkgo biloba extract manufacturer (including the extract manufacturer without the drug production license) and the Ginkgo biloba drug preparation manufacturer shall, in accordance with the supplementary inspection standard, check the Institute of the company since January 1, 2014 There are Ginkgo biloba extract, Ginkgo biloba leaf and Ginkgo biloba leaf capsule for self inspection one by one; ③ all enterprises that use Ginkgo biloba extract to produce health food shall carry out self inspection immediately according to the production process and quality standard of Ginkgo biloba extract registered and declared On June 10, law enforcement inspection was carried out for the enterprises using ginkgo biloba extract to produce health food On August 10, the supplementary test methods for free quercetin, kaempferol and isorhamnetin in Ginkgo leaf soft capsule, dropping pill, Shuxuening injection and ginkgo leaf extract injection, ginkgo Damo injection and ginkgo leaf drops, and for Sophoricoside in Ginkgo leaf extract, ginkgo leaf and ginkgo leaf capsule were promulgated On September 10, the third phase of special supervision and sampling of Ginkgo biloba drugs was carried out In order to provide technical support for the follow-up investigation and handling of Ginkgo biloba drug cases, the non-conforming drugs detected should be inspected according to the supplementary inspection method of Sophoricoside inspection items on the basis of the special supervision and sampling inspection of Ginkgo biloba drugs in the first and second stages 1.2.2 special supervision, self inspection and sampling inspection of Ginkgo biloba drugs CFDA announced the inspection of drugs On June 22, 90 manufacturers of Ginkgo biloba extract, Ginkgo biloba leaves (including dispersible tablets) and Ginkgo biloba leaves capsule carried out self inspection of 5161 batches of products, and unqualified products 2335 batches, accounting for 45% of the total batch; 55 enterprises (61.1%) are unqualified products, 30 of which are unqualified products (33.3%), and 25 of which are unqualified products (27.8%) On July 2, 284 batches were randomly inspected in the first batch, among which 67 batches of unqualified drugs were detected, accounting for 23.6% of the total products, involving 24 drug manufacturers On July 31, 118 batches (60.8%) of the 194 batches of drugs sampled in the second batch were unqualified, involving 31 drug manufacturers 102 batches of drugs from 29 enterprises are unqualified in self inspection, and the results of sampling inspection are consistent with those of self inspection 16 batches of drug enterprises of 4 enterprises passed self inspection and the results of supervision sampling inspection were unqualified After in-depth investigation, it is confirmed that Heilongjiang Tianhong Pharmaceutical Co., Ltd., Jilin Province cross sea Biochemical Pharmaceutical Manufacturing Co., Ltd and Ningbo Lihua Pharmaceutical Co., Ltd have illegal behaviors of exchanging retained samples, falsifying evidence and evading supervision On September 8, it was found out that Hubei noon Pharmaceutical Co., Ltd reported false self inspection results, forged batch production inspection records, and exchanged retained samples, resulting in CFDA's notice on self inspection of 90 Ginkgo biloba extract and Ginkgo biloba drug manufacturers (No 24, 2015) listing the enterprise as all qualified enterprises in self inspection On October 15, 168 batches of samples were tested, including 38 batches of ginkgo leaf soft capsule, 24 batches of ginkgo leaf drop pills, 62 batches of Shuxuening injection, 7 batches of ginkgo leaf extract injection, 36 batches of ginkgo leaf Damo injection and 1 batch of ginkgo leaf drop Among them, 16 batches of unqualified ginkgo leaf soft capsules were detected, including 3 unqualified drug manufacturers, 13 batches of unqualified ginkgo leaf dropping pills and 1 unqualified drug manufacturer No unqualified products were found in Shuxuening injection, gingko leaf extract injection, gingko Damo injection and gingko leaf drops On October 15, out of 185 batches of unqualified Ginkgo biloba drugs detected in the first and second stages, 125 batches of drugs detected Sophoricoside, involving 27 enterprises suspected of illegally adding or using the illegally added Ginkgo biloba extract for the production of Ginkgo biloba drugs The unqualified rate of self inspection is 45% Based on the two-stage special supervision and sampling of Ginkgo biloba drugs, 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 most drug manufacturers were reliable 57 drug manufacturers are involved in the self inspection and spot check of unqualified drugs, accounting for 62% of all the inspected enterprises The detection rate of Sophoricoside was 67.6%, involving 27 enterprises The unqualified rate of ginkgo leaf soft capsule was 42.1%, ginkgo leaf dropping pill 54.2%, Shuxuening injection and other three injections were not found unqualified products 1.2.3 CFDA specially supervises the situation of health food and informs the self inspection of health food On July 3, 168 enterprises using ginkgo biloba extract to produce health food reported the self inspection situation Among them, 157 enterprises used ginkgo biloba extract to produce health food, and self inspected 359 batches of Ginkgo biloba extract raw materials, of which 328 batches were qualified, 13 batches were unqualified, and 18 batches were still under inspection; the unqualified Ginkgo biloba extract raw materials involved 8 health food enterprises On July 7th, 203 enterprises using ginkgo biloba extract to produce health food were investigated Of the 129 enterprises in production, 12 purchased raw materials using unqualified Ginkgo biloba extract 5.94 tons of suspected unqualified raw materials and 30.864 tons of unqualified health food were found in the inspection 1.2.4 see table 1-4 for the specific test results of Ginkgo biloba extract products According to the self inspection information of Ginkgo biloba extract products, all batches of products of 7 enterprises are unqualified in 53 batches; some batches of products of 8 enterprises are unqualified in 77 batches, qualified in 225 batches; all batches of products of 20 enterprises are qualified in 959 batches; a total of 1314 batches, total 130 batches, qualified in 1 batch 184 batches, 9.89% of which are unqualified batches, 20.00% of which are unqualified enterprises of all batches, 22.85% of which are unqualified enterprises of some batches, 42.85% of which are unqualified enterprises At present, there are 118 approval documents for domestic drugs of Ginkgo biloba oral preparation, among which nearly half of the enterprises are involved, 11 are involved in listed companies, affecting 247 health care products enterprises The market of Ginkgo biloba preparation with a scale of about 4.5 billion yuan was affected At the same time, the flow of problem drugs (health food) is complex, more than 20000 hospitals in 26 provinces and cities are affected, and there are hard to check health food sales terminals, so it is not easy to recall all of them 1.3 punishment CFDA issued the notice on punishment opinions on illegal production and sale of Ginkgo biloba extract and preparations (No 219, 2015) on November 5, 2015, and proposed the principle of classified punishment for illegal production and sale of Ginkgo biloba extract and preparations, as shown in Figure 3-5 (information source is from CFDA official website) Analysis and consideration of ginkgo leaf events 2.1 application and market 2.1.1 the modern development and Application Research of ginkgo leaf preparation started in Germany, mainly Acting on the brain, peripheral and other blood circulation disorders, which has a good effect on dementia, vascular dementia and Alzheimer's disease Ginkgo biloba extract preparation and health food is one of the most popular plant medicine products in the world market Incidence rate of every hue has been increasing China has been taking the ginkgo flavone and ginkgolides from the leaves of Ginkgo biloba leaves in 1960s The Ginkgo biloba tablets and Ginkgo biloba health foods and Ginkgo biloba extract products are full of market At least 130 countries around the world, such as Europe, are selling Ginkgo biloba extract preparations In 2013, Ginkgo biloba preparation