Zhongxin Jingwei, January 20 (Wang Yuling) Recently, the State Food and Drug Administration issued an announcement that it will stop the production, sales and use of Lianbizhi injection in China from now on, and cancel its drug registration certificate.
Lianbizhi is the first Chinese medicine injection to be stopped by the State Food and Drug Administration, marking that the post-market evaluation of Chinese medicine injection has been opened, what is the impact of this on the future Chinese medicine injection market? In fact, the effectiveness and safety of Traditional Chinese medicine injections have been controversial for a long time, and in recent years, they have been subject to increasingly stringent supervision, including modifying the instructions, restricting medical insurance reimbursement, and key monitoring catalogues. So, how should the relevant companies respond?
Post-marketing evaluation opens
Zhongxin Jingwei found that the Lianbizhi injection ordered by the State Food and Drug Administration is a traditional Chinese medicine injection, which has the effect of clearing heat, detoxification, antibacterial and anti-inflammatory, mainly used for the treatment of bacterial dysentery, pneumonia and acute tonsillitis, the ingredient is sodium bisulfite andrographolide, and the route of administration is intramuscular injection and intravenous infusion.
Although the State Food and Drug Administration did not directly give the reason for the removal of Lianbizhi injection, in June 2018, the Beijing Municipal "Quarterly Report on Adverse Drug Reaction Monitoring (Q1 of 2018)" stated that manufacturers and relevant regulatory departments should further strengthen the monitoring of adverse reactions of Lianbizhi injection and re-evaluate the drug if necessary to ensure the safety of clinical medication.
According to the announcement of the State Food and Drug Administration, the post-market evaluation of Lianbizhi injection was carried out this time. As a result, Lianbizhi has also become the first Chinese medicine injection in China to be ordered to be delisted by the State Food and Drug Administration. Many industry insiders said that this may become a "turning point" for Chinese medicine injection products.
In 2017, the General Office of the CPC Central Committee and the General Office of the State Council issued the Opinions on Deepening the Reform of the Review and Approval System and Encouraging the Innovation of Pharmaceutical Medical Devices, which clearly stated that in the future, the review and approval of drug injections will be strict, and the re-evaluation of drug injections on the market will be carried out. But in reality, it has not been executed.
The so-called post-marketing re-evaluation, that is, through the monitoring of adverse drug reactions, drug epidemiological investigation and clinical trials, the efficacy of drugs in the process of use, adverse reactions, drug interactions, medication status of special populations and drug risk/benefit ratio are monitored and evaluated.
What does it mean if Chinese medicine injection products are widely opened for marketing and then evaluated? Professor Guo Ruichen of Qilu Hospital of Shandong University commented on Zhongxin Jingwei that the delisting of Lianbizhi Traditional Chinese Medicine Injection may not be an isolated case, and if the post-market evaluation is opened, there will be more non-compliant products facing delisting in the future.
"If Chinese medicine injections do not keep pace with the times and improve their quality, they are still eliminated by extracts (doped mixtures, unknown ingredients), which are certainly not recognized and accepted by doctors and patients." However, it cannot be said that it is a non-conforming product, but it can only be said that the quality standard is improving, and it is measured as a non-conforming product with the new standard, which is the characteristic of the times, or the limitation (according to the registration, production, and quality standards at that time, it is a qualified product). Guo Ruichen added.
What is the impact of pharmaceutical companies?
In recent years, the State Food and Drug Administration has been strengthening the supervision of Traditional Chinese medicine injections, including modifying the adverse reactions, contraindications and precautions in the instructions, limiting the scope of application of medical insurance reimbursement, listing in the key monitoring catalogue, and strict management of auxiliary drugs. Under a set of "combination fists", the sales growth rate of traditional Chinese medicine injections has declined.
According to the data provided by the health industry data platform Zhongkang CMH, from 2017 to the first three quarters of 2021, the sales of Chinese medicine injections at hospital terminals (only public hospitals above the second level, excluding primary medical and private hospitals) declined rapidly, from 56.9 billion yuan in 2017 to 33.5 billion yuan in 2020, and sales in the first three quarters of 2021 were only 24.9 billion yuan; in the retail pharmacy market, the sales of Chinese medicine injections fluctuated at a low rate. In 2017, it was 153 million yuan, in 2020 it was 147 million yuan, and sales in the first three quarters of 2021 were 84 million yuan.
After the post-market evaluation is opened, pharmaceutical companies will also face a new round of challenges as more non-compliant Chinese medicine injections are removed from the shelves. For example, according to the announcement of the State Food and Drug Administration, there are currently three domestic enterprises with the approval number of Lianbizhi injection, namely: Wuxi Jiyu Shanhe Pharmaceutical Co., Ltd. (hereinafter referred to as Jiyu Shanhe), Shenwei Pharmaceutical Group Co., Ltd. (hereinafter referred to as Shenwei Pharmaceutical), and Jiangsu Jiuxu Pharmaceutical Co., Ltd. (hereinafter referred to as Jiuxu Pharmaceutical). Zhongxin Jingwei found that at present, the three companies cannot retrieve the relevant content of Lianbizhi injection.
Under the pressure of compliance and market, some pharmaceutical companies have begun to transform. Zhongxin Jingwei combed and found that some enterprises began to gradually reduce the proportion of Traditional Chinese medicine injections and transformed into Western medicines and oral medicines. For example, Shenwei Pharmaceutical said in its 2021 semi-annual report that the Group's key development strategy is to expand the growth of oral preparations, and the sales ratio of oral products has reached 59.1% of the Group's overall sales.
CR Sanjiu said at the investor telephone exchange meeting that the company is actively responding to the impact of policies and continuing to optimize the business structure, first, the specialty business is guided by clinical needs, strengthening the evidence-based research of existing products, continuously enriching the product pipeline, after digestion, the proportion of traditional Chinese medicine injections is limited; second, the Sinopharm business takes formula granules as the core business and strengthens the layout of the whole industry chain; third, actively adjusts the anti-infection business.
There are also pharmaceutical companies that are increasing investment in research and development and strengthening research on safety. Zhongheng Group said in its 2020 annual report that the company's follow-up plan is to further strengthen evidence-based medical research on thrombosis, accelerate the re-evaluation of safety and efficacy, strengthen the basic and clinical research of thrombosis, and provide support for clinical use. Complete the standardization of thrombosis, continuously improve the quality of thrombosis products, and ensure the safety and effectiveness of clinical drugs. Strengthen academic promotion, improve doctors' understanding of thrombosis, and improve the safety of clinical use.
Shi Lichen, founder of Beijing Dingchen Management Consulting Co., Ltd., said in an interview with Zhongxin Jingwei that the transformation of Chinese medicine injection-related enterprises mainly has several directions: "First, convert Chinese medicine injections into oral products; second, do four phases of clinical trials, clarify their safety and efficacy and other related clinical data, so as to enter the clinical path; third, abandon Chinese medicine injections and switch to other categories, such as biological drugs, new proprietary Chinese medicines, medical aesthetic products, health care products, etc." ”
The compliance of Chinese medicine injections has yet to be solved
For a long time, the effectiveness and safety of Chinese medicine injections have been controversial. According to the National Annual Report on The Monitoring of Adverse Drug Reactions, in 2013, there were 121,000 cases of adverse reactions to drug injections, of which 5.6% were severe reports. In 2014, adverse reactions were reported 127 000 times, of which 6.7% were severe. The proportion of serious reports increased in 2015 to 7.7%. In the 2017 adverse reaction report of traditional Chinese medicine, injections accounted for 54.6%.
Kang Zhen, a visiting professor at China Pharmaceutical University, analyzed Zhongxin Jingwei and said: "The problem with Chinese medicine injections is that, first, Chinese medicine pays attention to the balance of yin and yang, the indications for a single drinking tablet are relatively vague, and Chinese medicine pays attention to the treatment of diseases with prescription drugs; second, the formula changes from traditional decoction to Western-style dosage form - injection, which may lose the advantages of the original formula; third, the process requirements of Chinese medicine injections are higher, and many ultra-fine particles need to be removed, so the principle of drug treatment is that it can be taken orally without injection, and can be injected without infusion. ”
Kang Zhen believes that if the clinical application of Traditional Chinese medicine injections lacks the theoretical guidance of Traditional Chinese Medicine, adverse reactions will increase, and the indications will be difficult to treat, so the market for such drugs may shrink under strict supervision.
In addition, from the perspective of including medical insurance, Kang Zhen pointed out that the Food and Drug Administration will be more stringent in the access of Chinese medicine injections, because the clinical application of many Chinese medicine injections cannot be a panacea, and medical insurance will think that this is a waste of money. "From the perspective of clinical application, the rational use of Chinese medicine injections should follow the theory of traditional Chinese medicine, rather than abuse, and it is necessary to pay attention to the theoretical guidance of traditional Chinese medicine." Kang Zhen said.
However, he also stressed that the use of Traditional Chinese medicine injections cannot be "killed with a stick", and for some difficult and serious diseases, critical and critical diseases, Chinese medicine injections still have good clinical effects.
In the view of Deng Yong, a professor at the Law Department of Beijing University of Traditional Chinese Medicine, Chinese medicine injection enterprises should re-evaluate the safety, effectiveness and quality controllability of Approved Chinese Medicine Injections in accordance with the relevant policies on encouraging the innovation of pharmaceutical medical devices and the implementation of the whole life cycle management of pharmaceutical medical devices (Draft for Comments) issued by relevant departments, in accordance with the relevant provisions of the Drug Administration Law of the People's Republic of China, and according to the scientific progress of Chinese medicine injections and drugs.
"For products that affect public health such as traditional Chinese medicine injections, the results of safety evaluation should be disclosed in a timely manner and translated into instructions, so that the risks are clear and the management is in place, so as to eliminate the public's panic and doubts as much as possible." Deng Yong said to Zhongxin Jingwei.
He also made relevant suggestions for the development of the Chinese medicine injection industry:
First, at present, the quality of new and old injections is unbalanced, the quality of mainstream enterprises and small enterprises is unbalanced, and the quality of original research plants and imitation factories is unbalanced. By raising the industry threshold, the production enterprises of traditional Chinese medicine injections should be reshuffled, and the enterprises with small scale, low technology and poor quality should be shut down and transferred.
Second, Chinese medicine injection manufacturers should strengthen cooperation with medical universities and medical science academies, strengthen the basic research of chemical substances contained in Chinese medicine injections, and accelerate the transformation of the results of Chinese medicine injection purification technology.
Third, some companies are reluctant to invest in adverse reaction monitoring (ADR) because they are reluctant to invest in large-scale centralized safety monitoring because they are concerned that the results of large-scale centralized safety monitoring may be shared. In this regard, different Chinese medicine injection manufacturers can cooperate to jointly increase the funds and personnel investment in the centralized monitoring of adverse reactions. At the same time, in the process of centralized monitoring of adverse reactions, it is necessary to establish a standardized clinical safety evaluation method. Break the thinking of using the New Drug Clinical Trial Specification (GCP) to look at centralized monitoring, and innovate the method of centralized monitoring.
Finally, establish a response mechanism for the safety incident of Chinese medicine injections. Once an adverse reaction event occurs, the enterprise should comprehensively carry out risk investigation and strengthen market monitoring; timely and effectively rectify the risk problems found; and immediately report to the relevant government departments if abnormal situations are found. (Zhongxin Jingwei APP)
(The views in this article are for reference only and do not constitute investment advice, investment is risky, and you need to be cautious when entering the market.) )
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Editor-in-Charge: Wei Wei
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