Long: Chinese preparations export dragon's plight.

Guide: The dawn will come come come when we are awake. Dawn will come only when we are awake - Thoreau Walden Lake.
article source:
. Sam Y
1994-2005 was a grey eras in the history of Chinese pharmaceuticals, and the origin of the backwardness of the level of Pharmaceutical preparations in China.
we have experienced a lack of medical care and medicine, when the government encouraged enterprises to invest in factories and try to solve the problem of drug accessibility. Now, with the development of economy and society, accessibility is no longer a problem, but the low level of repetition, serious overcapacity, has become a prominent contradiction in the pharmaceutical industry development.
quality management, more than 1,000 enterprises passed GMP certification in the three years from 1999 to 2002; What is not publicising in the industry is that at this time GMP certification has become a "commodity" that can be bought for money. Each GMP-certified pharmaceutical company, including hardware retrofitting and operating costs, paid an average of about $10 million. During this period, more than 6000 enterprises across the country through the GMP certification, and these enterprises GMP recertification once, is also an impossible task.
drug registration, the drug regulatory department in 2004 alone received 1009 "new drug" applications, while the U.S. Drug Enforcement Administration in the same period only received 148. In 2005, the FDA approved 11,086 applications for drug registration, 80 per cent of which were generic. This time the generic review rough, the same molecule entity, A generic drug reference to the original study, B generic drug reference A, C generic drug reference B, the more imitation is not like, should be consistent with the reference preparation prescription, the result of "one factory side", or even "one factory multi-party." Then because of the hospital's "one-product-to-two-rule" restrictions, the emergence of thousands of deliberately with the original drug different dosage forms, different doses, different salt roots, and even different molecular entities of the "characteristic improvement of drugs", without similar to the United States strict 505(b)2 approval, these drugs are considered clinically poorly verified, can also be close to the price of new drugs on the market. Between 2003 and 2005, only 212 brands were approved for independent intellectual property rights of chemical drugs, of which only 17 were genuine chemical entities, plus 22 Chinese medicines, accounting for only 0.39% of the "new drugs". It was not until 2008 that the FDA cleared the backlog of 24,000 applications from its predecessor, and the "heritage" of the cultural drugs still alive by the end of 2015 was about 17,000, about 8,400 Chinese medicines, while China's 167,000 generic drug approvals contained re-registered batches, a considerable part of which had the shadow of the Drug Registration Management Measures, which began to be implemented in 2002.
taken from lilac garden
to declare these approvals registration documents (commonly known as Dossiers), before 2010, is not the international common drug technology document Common Technical Document (CTD), but a set of not yet standardized Chinese characteristics documents, CTD documents are a carrier of the research and development process, but also on behalf of the pharmaceutical manufacturers have a pharmaceutical technology (Technology) proof that the lack of CTD module, the lack of pharmaceutical technology. From the perspective of CTD, irregularities are mainly reflected in the most critical module 3 pharmaceutical research part (Chemistry, Manufacturing and Controls, CMC) and module 5 clinical research bioequiency part (Bioequivalency, BE) is inadequate or missing, so these approvals and technical documents have not been recognized by the international community, to be exported, must be patched bit by bit.
is less full
on May 31, 2007 in the People's Daily and Xinhua News Agency special commentator article published the same content of the article, the title is "the people's interests above all else." The article points out that the central government "has always attached great importance to people's livelihood issues, and has always regarded the interests of the people above all as the starting point and the starting point for making policies and doing their work". The article is thought to have sounded the horn of the opening of the new era, albeit with a long road.
With the release of the 2010 "Chemical CTD format declaration data writing requirements", the concept of pharmaceutical generic technology documents was officially introduced in China, CTD is not only a simple application file format requirements, more like a research and development ideas, more is the combination of process control and endpoint control of the drug quality control concept, more is today's familiar QbD concept ( Design quality from the design) is an important embodiment of the content and research level of the research. Since then, our Dossiers have gradually moved closer to international requirements, and the concept was introduced internationally in Europe and the United States in 1989, ich
M4Q approved in December 2002. We are 20 years behind the SRA (
Regulatory Authority
, such as Europe and the United States, and 9 years later than the ASEAN countries that implemented the localization of THE ACTD in October 2010, or even years later than in some African countries.At the same time,
the State Bureau has also begun to improve the management of drug registration, which has been in the public for consultation over the years and will eventually be approved by the end of March 2020. We've seen efforts by China's pharmaceutical administration to make up for the dead sheep, but we've also seen the process of Dossiers catching up with rising international standards, because although the CMC portion of Module 3 has improved over the years, the BE part of module 5 has not improved significantly, and Chinese drugmakers have found imitations. The drug market does not strictly follow the drug clinical trial management code (Good
Clinical
Practice, GCP) can still be approved for listing, so not keen to do rigorous BE trials, saving money to invest in "feature modified drugs" to open the big IV phase or real-world research (real
world research,
RWR) clinical, evaluate the actual effect of these drugs on the market to achieve marketing and promotion, China's large number of clinical resources are still occupied by these RWR clinical trials, and these non-random, open, placebo-non-blind trials to evaluate these "feature improvement drugs" The effect of the review of history.
until the "clinical 722 massacre" occurred and the consistency evaluation of the full implementation. On July 22, 2015, the State Administration of Food and Drug Administration (CFDA) "State Food and Drug Administration on the implementation of drug clinical trial data self-checking and verification work" The State Administration of The State Bureau said in a notice: "The applicant self-checking the clinical trial data is not true, incomplete and other issues, can be submitted to the State Food and Drug Administration before August 25, 2015 to withdraw the registration application", the industry agreed that this announcement later thoroughly overhauled the new drug clinical trial and generic drug generic be. Then, on March 5, 2016, the CFDA forwarded the Opinions on the Evaluation of Quality and Efficacy of GenericS issued by the General Office of the State Council, and then the State published the List of Reference Preparations, which means that the curtain of the consistency evaluation (Consistency
Evaluation, CE), which has been in the pipeline for four years, has in fact been officially opened, and the oral preparations required by the prescription process are first scratched.
generic consistent evaluation refers to the approved generic drugs on the market, according to the principle of consistent with the quality and efficacy of the original research drug, the quality consistency evaluation in phases,
is that generic drugs need to achieve the same level in quality and efficacy as the original drug. ABC generics can only be compared to the original research drug for imitation, has been approved for the market of generic drugs for consistency evaluation, which is a lesson in the history of the study. Because in the past approved drugs did not have the mandatory requirements for consistency evaluation with the original drug, some drugs in terms of efficacy and the original drug there are some gaps. Historically, the United States, Japan and other countries have also experienced the same process, Japan spent more than ten years to promote generic drug consistency evaluation work. To carry out the consistency evaluation of generic drugs, can make generic drugs in terms of quality and efficacy consistent with the original research drug
, in clinical lying can replace the original research drug, which can not only save medical costs, but also improve the quality of generic drugs in China and the overall level of development of the pharmaceutical industry, to ensure the safety and effectiveness of public drug use. The evaluation of generic drug consistency is a complement and innovation in our country. To achieve the efficacy of the quality of the original research drug is consistent, not far from the creation of new drugs.
now we see the dawn of "domestic medicine" in line with international standards, but before that those not recognized, the drop of the course, need to invest in a country's medical resources and a long time to make up, but the past mistakes have led to the Chinese preparations in the process of going abroad facing the "three mountains" - GMP inspection (Technical Dossiers for License), cost (CoGS) trouble.
2
three mountains
crossthe the hills, only to find higher hills.
graduated from the Chinese Academy of Military Medical Sciences, long-term residence in the United States, the independent medical commentator Mr. Meng Eightyhas has pointed out: "China's generic drug preparations in developed countries, still difficult, so it is too early to talk about internationalization", the preparation export is one of the main purposes of the internationalization of pharmaceutical enterprises, but history has pressured three mountains to this industry, bearing the burden forward.
the first mountain is GMP inspection,
obtain edited GMP by foreign drug regulators, the process mainly depends on burning time. GMP (GoodManufacturingPractices, specifically the quality management practice sourcing drugs), is from the "human, machine, material, law, ring" five different perspectives to develop norms to control the production process of drugs, so that drugs meet the expected quality. China as a relatively strong API country, in the past few decades in the pharmaceutical industry development, accumulated a large number of GMP management personnel, their professional background from engineering, analysis, micro-organisms, there is (no) machine chemistry, these pioneers support Chinese pharmaceutical from scratch, from raw materials to preparations, China's GMP management has been progressing, but has not yet risen to the international mainstream society recognized the degree of Chinese preparations in the export process encountered the first problem is not trusted GMP.
Chinese pharmaceutical companies in the application and payment of expensive inspection fees, through a few months or years of queuing process, foreign drug regulatory agencies will come to China's factories, wearing colored glasses for 1-5 days of on-site audit, see that you meet the domestic regulatory requirements, the level of these inspectors is not necessarily higher than China, usually with the country's pharmaceutical industry level has a certain relationship, inspectors generally friendly For example, small countries in Asia and Latin America, inspectors have production practical experience and professional training, the level of China, if the country's pharmaceutical industry is underdeveloped, such as Africa sent inspectors mostly from the field of analysis, the defects are not very professional, and self-esteem, they use this opportunity to go abroad, in the process of inspection to learn the GMP concept of abroad, enhance experience, in addition to the drug regulatory agencies to generate income, individual inspectors in the inspection period can also receive more than several times the gift of wages. After the inspection, the inspector will submit a defect item, the pharmaceutical company will be required to submit a short time to submit a plan called CAPA (Pharmaceutical Production Correctionand and Preventive Measures, CorrectiveAction and PreventiveAction), and the deadline for rectification will usually take several months, and finally reach its pharmaceutical satisfaction before closing CAPA, and then obtaining a foreign GMP certificate (or through letter).
the second mountain is a
of technical document review, to prove to the reviewer that my pharmaceutical technology is developed in compliance and can stand the test. To obtain a foreign product registration certificate mainly by money and time together burning, with this foreign registration certificate can be listed overseas. In recent years, many countries' drug regulatory agencies have been the drug registration documents of the review, to the regulatory market, mainly to avoid overseas pharmaceutical companies can pass the GMP audit, and Dossiers can not pass the embarrassment of the review, to save drug resources. This side reflects that the height of the second mountain is actually higher.
1990s, WHO, globally, regulated and promoted the "passport" format for multi-generic generic sinfPs drug registration certificates, and if the drugs to be exported have obtained a national registration certificate in the country of origin, they can apply to their national drug regulatory agency for an internationally recognized "passport", i.e. a CPP or A. The 1997 version of the CPP includes a number of content, such as the name of the drug, dosage form, specifications, production plant, licensee, whether the production plant through the gmp inspection and other items. The purpose is very clear, with this certificate, on behalf of the drug has been in the exporting country through the evaluation and listing, to save the evaluation resources of importing countries, promote the global trade circulation of generic preparations, expand the economic downturn, the pharmaceutical industry backward countries access to medicines. At that time to obtain a non-regulatory, semi-regulatory market drug registration certificate, very irregular, only submitted some Chinese company qualification documents, such as business license, CPP, drug stability data under certain conditions, fill in some forms, and then pay to obtain overseas drug registration certificate after a few months, this ten years time China harvested a lot of overseas registration certificate, registration in the pharmaceutical enterprise sorority, some registration certificate has been successfully maintained to date, the most in China's pharmaceutical enterprises to continue to see the current
overseas regulators are slowly finding that only by raising the threshold for registration can they circumvent regulatory loopholes, such as pharmaceutical companies that buy chinese goods cheaply and do not list in China, in an attempt to escape the official supervision of China, and some illegal corporate fraud documents. At the beginning of the 20th century, some countries began requiring State Pharmaceutical Companies of Origin to prove that the drug is in a normal state of sale in China and must provide a Free Sales Certificate.