With the revision of drug registration measures, the imitation of traditional Chinese medicine will become a history

Recently, the National Drug Administration (nmpa) once again released to the public the measures for the administration of drug registration (Revised Draft for comments) (hereinafter referred to as the revised draft of the measures), which attracted a lot of attention One of the important changes attracted the attention of the author, but at the same time, it was found that people did not pay much attention to and discuss it I hope we can fully discuss it before the promulgation of the regulations On feedback In Chapter 1 and Article 5 (drug registration category) of the revised version of the measures, the registration of traditional Chinese medicine is divided into five categories: innovative drugs, improved new drugs, ancient classical Chinese medicine compound preparations, similar drugs of the same prescription, and overseas listed domestic unlisted traditional Chinese medicine Where is the traditional Chinese medicine generic? What is the "similar medicine of the same prescription"? What are the similarities and differences between traditional Chinese medicine and generic drugs? Is the research and development process as painful as biological analogues? In the revised version of the method, there are only five words of "the same prescription is similar to medicine", without any explanation and explanation, the author can only find another way to see the truth It is stated in the exposure draft of the measures for the administration of drug registration (Revised Draft) in 2017 that: "generic drugs should be consistent with the quality and efficacy of the original research drugs or reference preparations; biological similar drugs and similar drugs of the same side should be comparable with the quality and efficacy of the original research drugs or reference drugs"; and then from the requirements for registration classification and application data of traditional Chinese medicine and natural drugs attached to the 2017 exposure draft（ Find the definition of similar medicine of the same side (4 types of traditional Chinese medicine registration) "similar medicine of the same side refers to the medicine with the same prescription, dosage form and daily crude drug quantity as the traditional Chinese medicine or natural medicine already sold on the market, and similar to the traditional Chinese medicine or natural medicine in terms of quality, safety and effectiveness." It is relatively simple for generic drugs to achieve "consistency" and basically for pharmaceutical consistency and bioequivalence to meet the requirements; however, it is difficult to say that similar drugs "have the same quality and efficacy", and those that cannot be said clearly need to invest a lot of money and do a lot of research, including large clinical trials It is not much easier to make a biological analogue than to develop a new biological medicine Although the change of registration and classification of traditional Chinese medicine has directly turned the traditional Chinese medicine generic into history, perhaps the Chinese medicine researchers and researchers have been numb to this, and the traditional Chinese medicine generic has almost become history in fact A month ago, a friend wanted to copy a variety of traditional Chinese medicine and asked yaozhi.com to make a project research report I asked about his expectation and budget, but he didn't do the research I gave a direct suggestion: don't copy it It is more difficult and expensive to copy a traditional Chinese medicine than a chemical medicine, and the possibility of success is very small Why is it so difficult to copy a traditional Chinese medicine, and there are so many traditional Chinese medicine imitations in the market? Let's first look at the history of traditional Chinese medicine generics In the history of our country, the approval of "traditional Chinese medicine generic drugs" was very free and simple, especially during the cultural revolution, drug supervision and management was regarded as the pressure of management and the shackles of people's drug use Therefore, a county reform committee or a factory director can "approve" a drug to be listed on its own (such as generic drugs and new drugs), until the State Council approved and transmitted the "Regulations on Drug Administration (Trial)" formulated by the Ministry of health on July 30, 1978, which requires that "every drug produced by Chinese and Western drug manufacturers must be submitted to the provincial, municipal and autonomous region health bureaus for examination and approval Approval " At that time, there was a drug administration department under the provincial and municipal health bureaus, although it was just a department under the provincial and municipal health bureaus, but it had the right to approve the production of generic drugs The drug administration measures issued in 1985 even stipulated in the form of laws: "to produce drugs with national or provincial standards, the provincial health administration department must solicit the opinions of the drug production and marketing departments at the same level See review and approval and issue approval number " It can be imagined that the imitation of traditional Chinese medicine at that time was still relaxed and pleasant Basically, as long as we can find a national or provincial standard for a drug, and can produce three batches of drugs that meet the standard, we can approve the listing There is another way to imitate traditional Chinese medicine Now many people have never heard of it It is called "transplantation of traditional Chinese medicine" In 1988, the Ministry of Health issued the notice on restoring the transplantation of Chinese patent medicine In order to protect some varieties from being imitated indiscriminately, in 1990, the Ministry of Health issued the notice on strengthening the management of varieties of Chinese patent medicine transplantation to strengthen the standardized management Different from the simple method of imitating the standard, when applying for transplanting a variety of Chinese patent medicine in the Provincial Department of Health (bureau), the transplanting unit must hold the original prescription, production process, quality standard and clinical research summary of the variety It was not easy to get these materials, but at that time, they were basically state-owned enterprises, and it was possible to develop the spirit of selfless dedication of the proletariat Another channel is that many Chinese patent medicines are successfully developed by scientific research institutes If there is any omission in the contract, the scientific research institutes can "marry two women" and sell the materials to another manufacturer for production This situation was maintained until the establishment of SDA in 1999, which concentrated the approval power of local drug production to SDA and opened a new chapter of drug regulation In 1985, 1992 and 1999, the new drug examination and approval measures only focused on new drugs, but did not include the examination and approval of generic drugs in the management In 2002, after the establishment of SDA, measures for the administration of drug registration (for Trial Implementation) was promulgated, and the registration of generic drugs was included in the regulatory system for the first time Generic drugs of traditional Chinese medicine have become the 11th category of traditional Chinese Medicine Classification in the measures: there are already national standards for Chinese patent drugs and natural drug preparations, and the basic requirements for such drugs are to reduce animal tests and clinical trials, which is also very loose for pharmaceutical research Although the right of approval of generic drugs was transferred to the State Food and drug administration, before 2007, the management of generic registration of traditional Chinese medicine was very loose, the prescription of traditional Chinese medicine was relatively complex, and there were many drug components Many R & D personnel blindly copied the standards of generic drugs without analysis and research Some even started to copy the drugs with unclear taste, prescription and technology The "measures for the administration of drug registration" has aroused the enthusiasm of traditional Chinese medicine manufacturers for imitation From the figure below, we can see that the rapid growth of traditional Chinese medicine generic drugs reached its peak in 2006 (up to 2738 acceptance numbers, with an average of more than 10 acceptance per working day) Although there are so many problems in the picture source "big data of China's pharmaceutical R & D for 40 years", objectively, it is still effective on the drug supply side, that is to say, there are many exclusive varieties, quasi exclusive varieties (few manufacturers) with more generic drugs, or the same varieties with different dosage forms Once there is a competitor of generic drugs, the high drug price will lower the noble head So in this sense, the medical insurance department should be grateful for the time when the traditional Chinese medicine generic drugs were approved every day However, benefiting from the national technology secret varieties, Chinese medicine secret varieties, Chinese medicine protected varieties, and the characteristic laws and regulations such as the standard can not be copied without being changed into a regular one, a large number of exclusive varieties are still lonely up to now After the madness, it is disillusionment As can be seen from the above figure, after the drug registration verification in 2006 and the introduction of the new administrative measures for drug registration in 2007, the application of traditional Chinese medicine generic drugs has declined precipitously, and it has been "lingering for a long time", with only a few generic drug applications every year In the figure below, the registration of 9 categories (green) means that the proportion of traditional Chinese medicine generic drugs has declined since it became the first one in 2008 In recent years, the number of applications for traditional Chinese medicine generic drugs is far less than that for traditional Chinese medicine new drugs (clinical and marketing) It can be seen how difficult it is to make traditional Chinese medicine generic drugs?! Note: Class 9 (green) is traditional Chinese medicine generic drug, class 6 (yellow) is compound new drug Since 2007, SFDA has strengthened the management and registration of traditional Chinese medicine generic drugs Generic drugs require research, development and production in accordance with the generic drugs (basic sources), prescriptions and processes However, such detailed information is difficult to obtain legally Moreover, clinical trials are carried out according to the needs of the situation, which greatly improves the difficulty of traditional Chinese medicine generic drugs There have been many enterprises trying to break through the barriers, but they have either repeatedly issued supplements or not approved them Some of them have obtained approval documents, but only clinical approval documents Thinking that they still need a huge amount of clinical investment and bear the huge risk of clinical failure, the boss has to silently lock the clinical approval documents in the archives It is a wonder that the number of generic drug applications is less than that of new drug applications Is there any problem in policy orientation? As far as technology is concerned, it is right to strictly control the access of drugs whose efficacy is not guaranteed to the market For example, because the original drug a has not been verified by systematic clinical trials of new drugs, and its effectiveness is questionable, the threshold for generic drug a to be put on the market is greatly increased However, in another way, because there is no generic drug a, it is an exclusive drug, which enters the medical insurance at a high price and sells on sale in the unique Chinese medical market It's better to approve its generic drug, at least the medical insurance and patients spend less After several years of competition, perhaps the market share of this drug has become very small In the past 10 years, the number of generic drug applications is too small, and there are fewer approved ones, which leads to the monopoly and semi monopoly of exclusive and quasi exclusive traditional Chinese medicine, and the price of traditional Chinese medicine remains high for many years On the one hand, some managers of traditional Chinese medicine enterprises complain about the "almost impossible to copy" generic drug policy, but on the other hand, they also secretly enjoy: "this policy binds their own hands and their competitors Although there is no patent for these exclusive varieties of our family, they enjoy a longer exclusive ownership than the patent, which may remain unchanged for 50 years." If you are poor, you will think of change If you change, you need to consider wisdom If we want to solve the problem fundamentally, we should carry out strict drug re evaluation However, based on the current situation, this is not possible at all, even the re evaluation policy of traditional Chinese medicine injection can not come out At present, there are two changes in the generic drugs of traditional Chinese medicine: first, the relevant policies of "ancient classic prescription of traditional Chinese medicine compound preparation" have been issued, and the administration of traditional Chinese medicine has issued the first batch of 100 classic prescriptions, of which about 10 prescriptions are the same as those of the products already on the market, quietly opening a door Unfortunately, the document issued by the State Food and drug administration stipulates that the existing listed varieties cannot be registered and declared as "classic prescription preparation", and it quietly closes the side door of "imitation" of traditional Chinese medicine, which lacks the temptation of "large varieties", and the enthusiasm of manufacturers to declare is not high It is hoped that after the revision of the measures for the administration of drug registration, it will be adjusted, and this restriction will be released, so that there will be similar competition among exclusive varieties It can also be regarded as "blocking" the imitation drugs and giving a "sparse" channel at the same time Another change is the cancellation of traditional Chinese medicine generic drugs as mentioned at the beginning of this article and the transformation into similar drugs of the same prescription According to the definition of name and concept, it is more difficult to declare the similar drugs of the same prescription than the generic drugs of traditional Chinese medicine If the clinical trials of similar drugs of the same prescription are really required according to the idea of biological similar drugs, this is an insurmountable mountain To talk about the characteristics, I think that the characteristics of traditional Chinese medicine can be fully considered in the similar drugs of the same prescription In the specific rules and guidelines issued later, a small door will be opened for the imitation of traditional Chinese medicine, so that the exclusive varieties of traditional Chinese medicine in the door will no longer be "alone" Statement: this opinion only represents the author and does not represent the position of yaozhi.com You are welcome to exchange and supplement in the message area If you need to reprint it, please note