The Chinese government has recently released a number of documents indicating its actions against pharmaceutical companies that have allegedly produced or re-sold adulterated, mislabeled, or otherwise improperly produced ginkgo (Ginkgo biloba, Ginkgoaceae) extracts, or manufactured finished products containing such extracts. The actions are in response to growing reports of this problem. Within a period of about 10 days in May 2015, and then again in July, the China Food and Drug Administration (CFDA) issued at least four regulatory documents related to the production, labeling, and sale of ginkgo extract.

The first regulatory action notice1 was issued on May 19. The document detailed the results of the CFDA’s recent inspections of facilities of companies offering “low-cost” ginkgo extracts and noted that some “serious illegal problems” were found.

The bulletin stated that an inspection of the Guilin Xingda Pharmaceutical Co. Ltd. detected the use of inappropriate solvents in the manufacture of ginkgo extract. The company allegedly used 3% hydrochloric acid (HCl), instead of ethanol and water. It also allegedly purchased ginkgo extract illegally from an “unqualified” enterprise to produce ginkgo tablets and sell the purchased extract to another drug manufacturer. In addition, the company allegedly made false raw material purchasing records, false batch production records, and false batch test records.

In the same notice, the CFDA documented problems with the Wanbangde (Hunan) Natural Pharmaceutical Co. Ltd., which reportedly purchased ginkgo extract to produce ginkgo tablets and capsules, while also allegedly creating “fake raw material purchasing” records and false batch production and batch test records.

The regulatory agency noted that the actions of both companies violate Article 9, Article 32, and other provisions of the Drug Administration Law of the People’s Republic of China. The actions also violate the “Ginkgo Biloba Leaf Extract” standards of the Pharmacopoeia of the People’s Republic of China.2 The CFDA explained that the use of HCl can “decompose the effective constituents of medicine and affect the curative effect of medicine.”¹

As part of its investigation and regulatory action, the CFDA asked for all parties to discontinue the sale and use of ginkgo medicines produced by these two companies [Guilin Xingda Pharmaceutical Co. Ltd. and Wanbangde (Hunan) Natural Plant Pharmacy Co. Ltd.]. The provincial Food and Drug Administrations (FDAs) of Guangxi and Hunan provinces were instructed to monitor these enterprises and to recall the products in question. The FDAs of other provinces and autonomous regions were said to be responsible for recalls in their respective areas.

The investigation found that 24 drug manufacturers illegally purchased ginkgo extract from Guilin Xingda Pharmaceutical Co. Ltd. Regulatory authorities were instructed to review these companies and take immediate action, including recall of affected products. The authorities also advised all manufacturers of ginkgo extract and ginkgo extract preparations to conduct immediate internal examinations to determine if any of the previously noted irregularities could be found. Companies were given a deadline of May 24 to report to local FDA offices, cease all “illegal behaviors,” recall any affected products, and seal all equipment, raw materials, inventory, and related purchasing, production, and sales records.

Finally, the first notice stated that the CFDA will conduct a “comprehensive inspection of Ginkgo biloba preparations on sale in the market.” It will also inspect “some enterprises” — with violators subject to punitive action — and publish the results.¹

In the second notice published on May 20, the CFDA notified all regulatory parties in China of its investigations of Guilin Dayao Ye Ltd. “and other enterprises which illegally manufactured and sold Ginkgo biloba drug,” instructing regulatory agencies to carry out inspections and related regulatory actions.3 Such actions include taking “effective measures to stop any [further] use of these products, to effectively recall all the products in place,” with appropriate reporting to local regulatory agencies and the CFDA General Office.

Per the notice, the CFDA required local regulatory agencies to inspect all 24 pharmaceutical manufacturers that purchased ginkgo extract from Guilin Xingda Pharmaceutical Co. Ltd., and to recall any ginkgo extract materials produced with diluted HCl. It also required any information on such actions to be sent to all relevant provinces, autonomous regions, municipalities, and to the General Office. According to the document, companies found to be operating illegally that did not respond appropriately would “be dealt with severely and strictly.”³

On May 29, the CFDA issued a short announcement concerning the results of surprise inspections of Shenzhen Neptunus Bioengineering Co. on May 21 and Ningbo Liwah Pharmaceutical Co. Ltd. on May 23. The inspection of Ningbo Liwah Pharmaceutical Co. Ltd., which supplies Shenzhen Neptunus Bioengineering Co. with ginkgo extract, revealed that the company had purchased ginkgo extract from eight companies — although the document lists only seven — that the CFDA deemed “unqualified” (i.e., the extract was either adulterated or produced using an improper manufacturing process).⁴

According to the CFDA, Ningbo Liwah Pharmaceutical Co. Ltd. purchased ginkgo extracts and tested them using Chinese pharmacopeial methods and their own business standards, then added their name to the extracts’ labels. The CFDA document stated that the company sold these ginkgo extracts to Shenzhen Neptunus Bioengineering Co., Yangtze River Pharmaceutical Group Co. Ltd., and other companies (not named) for use in the production of drug products, and also to Wuxi Giant Pharmaceutical Co. Ltd. and others for use in the production of functional foods.

The document also noted that the Guangdong FDA instructed Shenzhen Neptunus Bioengineering Co. to stop producing related ginkgo products and that the agency would continue its investigation. The Zhejiang FDA reportedly made another inspection of Ningbo Liwah Pharmaceutical Co. Ltd. and opened a case for further investigation.

The CFDA’s announcement on July 7 reported that 203 companies in China had registered health foods (also referred to as “blue hats,” since the logo resembles a blue hat) containing ginkgo extracts.⁵ Among them, 129 enterprises were in operation, while 74 companies had stopped producing ginkgo extract-containing health foods. Of the companies in operation, 12 used unqualified ginkgo extract raw materials. An inspection found 5.94 metric tons (MT) of unqualified raw material, of which 2.28 MT had been used, 1.37 MT had been destroyed, and 2.29 MT were in quarantine. The investigation also found 30.9 MT of substandard finished dietary supplement products, of which 10.4 MT had been recalled, 0.023 MT (24 kilograms) had been destroyed, and 20.4 MT had been quarantined.

Twelve companies were found to have bought substandard ginkgo raw material from nine suppliers. Companies that manufacture or sell ginkgo ingredients and products are required to verify the quality of their materials and report the results to the CFDA. At the same time, provincial FDA branches were asked to continue the inspections and to report the findings to the CFDA by August 10.⁴

It is not clear to what extent, if any, the ginkgo extracts and finished ginkgo products made by the companies noted above may be exported to the international botanical market. Reports from the past 13 years document adulteration of various commercial samples of ginkgo extracts.^6-16

According to various insiders who are aware of the state of the ginkgo extraction industry in China, the issue of whether Chinese ginkgo extracts are being exported to the United States is particularly complicated. First, the CFDA’s actions targeted companies that produce ginkgo-containing pharmaceutical products and/or registered health foods. These producers are approved and qualified by the CFDA, and some export ginkgo extract to the US and other countries. According to industry sources, the CFDA has no authority over raw materials and extracts sold overseas; therefore, it seems as if the current regulatory event in China does not cover exports from CFDA-approved ginkgo raw material and extract producers. Further, a large number of ginkgo extract producers in China manufacture extracts for overseas markets only. These producers reportedly are not subject to any Chinese government agencies’ supervision. Therefore, the quality of the extracts from these companies may be more suspect than those under the supervision of the CFDA.

According to Cal Bewicke, CEO of Ethical Naturals Inc., a San Anselmo, California-based importer and marketer of supplier-qualified herbal extracts, including ginkgo, in order to sell ginkgo products at retail in China, a company needs a pharmaceutical license and must also buy ginkgo leaf raw material from suppliers with pharmaceutical licenses (email, July 4, 2015).

The companies mentioned by the CFDA in its investigations and notices are pharmaceutical companies selling to the Chinese retail market, or pharmaceutical manufacturers selling ginkgo extract to these companies to make tablets, capsules, or liquid, Bewicke noted.

“Many of the problems mentioned in the reports from [the] CFDA have to do with these companies buying materials from unlicensed sources, falsifying documentation to cover this up, and in one case, using HCl as a solvent,” Bewicke added. “They are not directly linked to adulteration problems in material supplied to the US market. However, the extent of the problems noted in these investigations underlines once again the importance of real supply chain custody documentation, supported by a full US-based testing program for all imported ginkgo extracts.”

—Mark Blumenthal

References

1. Announcement of the China Food and Drug Administration about the illegal production and sale of ginkgo leaf products by the Guilin Xingda Pharmaceutical Company Ltd. and other companies [in Chinese]. Beijing, China: China Food and Drug Administration; May 19, 2015. Available at: www.sda.gov.cn/WS01/CL0087/119540.html. Accessed October 13, 2015.
2. Chinese Pharmacopoeia Commission. Pharmacopoeia of People’s Republic of China. Vol 1. Part 1. Beijing, China: China Medical Science Press; 2010.
3. The notification to carry out special administrating of Ginkgo biloba drug products [in Chinese]. Beijing, China: China Food and Drug Administration; May 20, 2015. Available at: www.sda.gov.cn/WS01/CL0844/119541.html. Accessed October 13, 2015.
4. The result of the unannounced inspection for Shenzhen Neptunus Bioengineering Co. and Ningbo Liwah Pharmaceutical Co. Ltd. [in Chinese]. Beijing, China: China Food and Drug Administration; May 29, 2015. Available at: www.sda.gov.cn/WS01/CL0087/120400.html. Accessed October 13, 2015.
5. Announcement of the State Food and Drug Administration on the use of Ginkgo biloba extract on the production of health food companies troubleshoot situations [in Chinese]. Beijing, China: China Food and Drug Administration; July 7, 2015. Available at: www.sfda.gov.cn/WS01/CL0050/123540.html. Accessed October 13, 2015.
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