Speech Delivered by Comrade Bi Jingquan at the Founding Conference of the 11th Chinese Pharmacopoeia Commission
(August 29, 2017)
Today, we are here to hold the founding conference of the 11th Chinese Pharmacopoeia Commission and its first plenary session. On behalf of the China Food and Drug Administration, I would like to convey my congratulations for this conference and extend my sincere greetings to all the commission members, especially the members newly elected!
The main tasks of this conference are to: to arrange the compilation work of the 2020 edition Chinese Pharmacopoeia, to promote the drug standard reform, to strengthen the whole process administration of the drug standard and to further improve the quality of drugs. Here are some observations.
I. Fully recognizing the vital importance of the drug standard
The pharmacopoeia is the quintessence of the scientific and technological development achievements of drugs, the symbol for the development level of the drug industry of a country, the basic standard for the pharmaceutical manufacturers and distributors and the criterion for the drug administration work. Since the 18th CPC National Congress, Xi Jinping, the General Secretary of the CPC Central Committee, has emphasized for many times that “the most stringent standard, the most rigorous administration, the most severe punishment and the most serious accountability system” should be put into practice to ensure the food and drug safety of the people. General Secretary Xi Jinping puts “the most stringent standard” at the first place, and it highlights that the standard is of significant importance for the drug administration work. He also stresses, “The one who establishes the standard will have the voice; the one who grasps the standard will occupy the commanding height”. It deeply elaborates that the standard plays a decisive role for the product quality. Premier Li Keqiang also emphasizes that we should be determined to improve the drug quality and strictly observe each defensive line from the lab to the hospital.
The CPC Central Committee and the State Council attach great importance to the drug standard work. In 1949, when the People’s Republic of China was just established, the experts were organized to compile the new Chinese pharmacopoeia and the drug standardization was regarded as a strategic measure to change the backward situation of the weak pharmaceutical industrial basis and the few doctors and little medicine for the masses. In 1950, the Pharmacopoeia Commission of the People’s Republic of China was set up, and it became the first standardization organization of the New China. In 1953, the first edition Chinese Pharmacopoeia was issued. After the reform and opening-up policy was implemented, the legal status of the drug standard and the legal responsibilities of the Chinese Pharmacopoeia Commission are clearly defined in the Drug Administration Law. The Chinese Pharmacopoeia should be recompiled every five years. The drug standard work and the compilation and modification of the Chinese Pharmacopoeia are legalized.
Thus far, China has issued ten editions of Chinese Pharmacopoeia. The drug standard develops from nothing, from few types to many types, from low level to high level. They play important roles in improving the drug quality level of our country and promoting the transformation and upgrading of the pharmaceutical industry. The previous Pharmacopoeia Commissions made great contributions. We have greatly raised the drug safety standard, strengthened the drug safety administration, and no major or serious drug incidents have taken place in recent years. All of these should be affirmed fully. However, we also have to notice the backward industrial development, the poor regulatory capacity of the government, the failure of the drug standard to meet the requirements of the administration and the gap with the expectations of the masses due to the limited historical conditions. There are gaps between the drugs’ quality and efficacy of our country and those of the America, European countries and Japan, largely because the drugs are of low listing standard and there are insufficient branded drug in the market for reference. Such problems as the shortage, backwardness, unavailability, insufficient performance of the standard also exist to some extent. We should conscientiously carry out General Secretary Xi Jinping’s instructions on the drug administration work, speed up the standard formulation and modification, set up the scientific, complete, verifiable and executable standard system and improve the quality and efficacy of drugs with “the most precise standard” to prevent the drug safety risks and lay solid foundation for the drug administration work.
II. Some Issues Needed to be Studied Carefully
As the new Pharmacopoeia Commission has been set up, and the compilation of the 2020 edition pharmacopoeia has been launched completely, I would like to ask each member to study some issues together. These issues are of great importance for the standard formulation, the law revision, the promotion of reform and the administration enhancement.
(I) Studying the positioning of the pharmacopoeia work. The compilation of the pharmacopoeia should be carried out by implementing the development thought of being centered on the people, serving the drug administration, serving the reform and innovation and serving the development of the pharmaceutical industry. The purpose of compiling the pharmacopoeia to promote the high-quality drugs, eliminate the poor-quality drugs and identify the substandard and counterfeit drugs.
(II) Studying the essence of the modern drugs and the traditional drugs as well as their differences. The requirement that the state should develop the modern medicine and the traditional medicine is stated both in the Constitution of the People’s Republic of China and in the Drug Administration Law. The basic concepts of the modern drugs and the traditional drugs should be studied to clearly heir connotation and extension.
The concept of drugs came into being in ancient times. Every nation has its own traditional drugs historically. The traditional Chinese medicine culture of our country is extensive and profound and has played an important role in the lives of the Chinese nation and its struggling against diseases. The said age that we have ever lacked of doctors and medicines mainly refers to the age that we were short of modern doctors and medicines.
The modern drugs came to China with the modern medical science. The modern drugs gradually have the current basic characteristics on the basis of the traditional drugs and in combination with the modern evidence-based medicine: based on the theories of medical science, chemistry, biology and the like; generally having defined active ingredients and continuously studying and perfecting its functioning mechanism; going through the random and double blind clinical trial with large-scale samples, being proved effective on some indications by the test data, with benefits for the prevention or treatment of the certain disease of an individual patient or the human society larger than the risks. So the drug evaluation should be led by the clinical trials with the reviewer with the clinical doctor background as review team leader. In addition, there should be the production methods and processes approved by the regulatory authority to guarantee the uniform and consistent quality; for the overall supervision of the drugs, the marketing authorization holder should be responsible for the whole life circle of drugs, implement post-marketing studies, monitor adverse drug reactions and improve the understanding of drugs, including the side effects, contraindications, announcements and so on stated in the package insert; standardizing the continuously evaluating and market withdrawing system of the market drugs..
The traditional drugs, used for many years and accepted by the public, are the drugs adopting the traditional dosage form and usage, traditional indication expression, traditional evidence-based methods under the guidance of the traditional medicine theory and the traditional preparation methods. The traditional Chinese medicine theory is the cultural treasure of the Chinese nation, and we must carry forward, inherit and develop it. The most important distinction between the modern drugs and the traditional drugs lies in the evidence of the double-blinded random clinical trials with large-scale samples, indication conclusions with more benefits than risks, as well as uniform and stable quality control of products. In recent years, we have made great achievements in studying and developing the traditional drugs in the way for the modern drugs, and some important achievements have been made. The discovery of the artemisinin, berberine and ephedrine, especially the discovery of the artemisinin, constitutes our great contribution to the human community. We have also achieved remarkable fruits in treating leukemia with arsenic trioxide, which is a result drawing the global attention. We should carefully summarize our experience and lessons in the development and study of the natural drugs, including the outcomes acceptable clinically and recognized internationally and the lessons and faults. All of them are of significance for our inheriting and developing the traditional drugs.
(III) Studying the relation between new drug marketing standard, the orange book and the pharmacopoeia. According to the regulatory concept and practices of modern drugs, approving a kind of innovative drug is approving the standard for such drug, including the active ingredients, formula, the administration route, the dosage form, the specifications, the usage, the technique and the technological parameters as the business secret of an enterprise. All of these are also the criteria for post-market regulation of products. Enterprises must manufacture drugs in accordance with the approved standards, and the data of the whole production process should be authentic and complete, recorded in time and traceable. Otherwise, punishment will be made for adulterated drugs. The new drugs approved by the regulatory authority characterize the originality and the standard, and the patents applied for them are protected by the patent law. After the patent expires, the enterprises applying for the generic drugs can make use of the reference listed drug enterprises’ results and data, and the clinical trial with large-scale samples can be avoided. The regulatory authority reviews their pharmaceutical equivalence and biological equivalence in accordance with the standard of the reference branded drug, and if both of them are equivalent, the efficacy will be deemed equivalent and they can replace each other clinically. The above reference branded drug approved to be marketed and regarded as the reference product and the generic drugs evaluated for its efficacy equivalence are included in a directory set. The set is upgraded in a timely manner, and makes up the orange book system internationally. We also should establish the Chinese orange book system. We should study the relation between the new drug marketing standard, the orange book and the pharmacopoeia and their roles.
To some extent, the compilation and revision of pharmacopoeia are review and verification for marketed drugs. Review about authenticity, reliability, scientificity shall be made for recording, renewal and revision of the contents to assess safety, effectiveness and quality controllability. In case of doubt about authenticity, reliability, scientificity, safety, effectiveness and quality controllability, drugs that have not been produced for many years, drugs without adverse effect inspection for many years after coming into the market, handling suggestion and advice shall be proposed to the supervision department. Committee members shall maintain strict standards in revising pharmacopoeia, because it is the responsibility to the public and to the committee of experts.
(IV) Reform results shall be embodied in revising pharmacopoeia to serve reform and innovation. Decisions and arrangements of the Party Central Committee and the State Council have been fully implemented by China Food and Drug Administration to carry forward reforms on assessment and approval of drugs in cooperation with relevant departments since 2015. Not limited to assessment and approval, the reforms have been developed into comprehensive reforms on supervision system of drugs.
Why should we carry out the reform? First, although drug accessibility has been basically solved, gap still exists in quality and efficacy. Second, there are problems in development, production and distribution of drugs. Untrue and incomplete data in development, unauthorized changes in techniques, adulteration, jerry-building and incomplete, untrue, unreliable and untraceable data in production process, exaggerated advertisement and brag without scientific basis in distribution process have frequently emerged despite repeated prohibition. Third, assessment and supervision capacities are weak. Compared with rapid development of pharmaceutical industry, we are seriously short of supervisors. Due to scarce capacity, it is hard to exercise effective supervision, which causes many loopholes and blind space. Although existing problems have been found, the solutions are beset with difficulties. So it is unable to do what we hope to do. Fourth, the application has been overstocked due to low efficiency. This is an inevitable result because of the above three problems.
How should the reform be exercised? A series of important decisions have been made by the Party Central Committee and the State Council. Opinions on Reforming Review and Approval System of Drugs and Medical Devices (GF  No. 44) was published by the State Council in August 2015. Piloting drug marketing authorization holder system was approved by Standing Committee of the National People’s Congress in 10 provinces and municipalities in November 2015. Opinions on Consistency Assessment for Quality and Efficacy of Generic Drugs (GBF  No. 8) was published by General Office of the State Council in February 2016. National Drug Safety Planning in the 13th Five Plan (GF  No. 12) was published by the State Council in February 2017. Opinions on Deepening Reforms of Assessment and Approval System to Encourage Innovation in Drugs and Medical Apparatus was deliberated and approved by the Central Leading Group for Comprehensively Deepening Reforms in July 2017. With approval of the State Council, we joined International Conference on Harmonization (ICH). Then we will strive to join Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (PIC/S).
The overall goal of reforms is to be geared to international standards. The basic standard for new drugs to be marketed is to be global new and generic drugs shall have the same quality and efficacy with original drugs. Drug data protection system, patent compensation system and drug review and patent linkage system shall be established with solution of patent disputes prior to drug marketing. Both drug innovation and innovators shall be encouraged and imitation shall also be encouraged to reduce imitation cost and legal risks of enterprises. Team assessment system, conference communication system with applicants, liaison system between project managers and applicants, expert consultation committee publicly demonstrating major disputes system, assessment results and bases disclosure system shall be established with clinic as leading to guarantee justice and equity of the assessment. Drug life cycle management shall be achieved to realize supervision in development, processing, distribution and utilization. Holders of drug approval documents shall take the legal liability for drug life cycle, including development, processing, distribution, adverse effect supervision and drug quality perfection. Application with untrue, incomplete or untraceable clinical trial data shall be revoked. Serious treatment shall be made for production process violating GMP and untrue, incomplete or untraceable data with treatment results disclosed to the public. Criminal responsibility shall be lawfully investigated for law breakers such as those counterfeiting. The system for reviewer, inspector, tester and law enforcement officer to keep business secrets of enterprises shall be established and the system for prohibiting staff from disclosing drug assessment information privately shall also be established. Staff shall be prohibited strictly from seeking personal gains from assessment, inspection and business secrets of enterprises. The authority of supervision shall be guaranteed with implementation of responsibility for secrets winning the trust of the people.
Reforms include assessment and approval for drugs to be marketed in the future as well as evaluation and clearing for drugs marketed in the past. Drugs fail in passing the evaluation within the specified period shall be withdrawn from the market. Long-term production halt, changing techniques randomly, defaulting duty of research and vigilance after marketing of drugs, problems in safety, efficacy and quality stability shall be cleared and corrected and those serious shall be withdrawn from the market. Standards, criteria and procedures for withdrawal of drugs from the market shall be formulated.
In a critical period of reforms, changes may occur to the compilation of the new pharmacopoeia. A series of requirements of the Party Central Committee and the State Council about assessment, approval and supervision reforms of drugs shall be implemented in the compilation of the pharmacopoeia to embody achievements of the reforms and reflect improvement in quality and efficacy of drugs promptly. I hope that members of the new Pharmacopoeia Commissionhold precise, scientific, impartial and objective attitude to participate in reforms actively, promote reforms and serve reforms. All employees, research workers and supervisors of the pharmaceutical industry are participants and impellers of the reforms. We shall actively promote matters conforming to interests of the masses and facilitating health of the public. While we shall decisively abandon matters not conforming to interests of the masses or not facilitating health of the public. All the work made by us shall be amenable to the history. While transforming the objective world, we shall also transform our subjective world to study new knowledge, master new skills, innovate system and mechanism, reinforce ability construction.
(V) It shall be studied how to break the latent rules of adulteration and counterfeit and serve the supervision in the compilation of the pharmacopoeia. Now it has been a kind of phenomenon that people will study to find methods of adulteration and counterfeit for cheating indexes specified in the pharmacopoeia. I hope that experts may find solutions to this issue based on your specialties to prohibit loopholes and break the latent rules.
III Some Requirements
Pharmacopoeia Commission is the most authoritative technical institution in pharmaceutical field of China and it takes the sacred mission vested by the party and the country to formulate national standards for drugs. The compilation of the pharmacopoeia is a task to help the patients. The 11th Pharmacopoeia Commission is officially established today. And it is a great honor and also a heavy responsibility to be members of the pharmacopoeia committee. All the members shall keep the mission and responsibility in your heart to successfully complete compilation of the pharmacopoeia with high responsibility.
First, adhere to scientific attitude. Coming from different fields and specialties, members shall respect each other and learn from each other with equal discussion. Precise style, pragmatic attitude and innovative spirit shall be put in the work.
Second, take responsibilities bravely. Various contradiction, difficulty and problem may appear in the revision of all standards and a choice may face different opinions. With people’s interests and health of the public as basic starting point, we shall dare to face problems directly and take responsibilities in order to solve problems. Then work achievements may be made by us without shame and guilt.
Third, reinforce system construction. Rules and regulations for standards shall be revised and standard work procedures shall be perfected. Besides, avoidance system for interest conflict, public demonstration system for major divergencies, public response system for substantial opinions not accepted shall be established to for democratic, scientific and public decision-making and social supervision.
Fourth, stick to disinterested professional ethics. It is the implementation of national public power to formulate and revise standards. Members of the pharmacopoeia committee must follow the laws and disciplines for national public servants. Party members of committee shall follow the spirit of eight-point rules and disciplines for them during practice of work. Others shall also follow the spirit of eight-point rules to stick to principles without malconduct for interests or personal relationship. Behaviors violating national laws and professional ethics shall be investigated and treated strictly with treatment results disclosed to the public.
All members and comrades, it is of great responsibility and glorious mission in making standards for drugs. We shall closely unify to the Party Central Committee with Chairman Xi as the core to adhere to people-oriented development and exercise the requirements of the Four Most Strict. With more scientific standards guaranteeing drug quality, supporting drug supervision and leading industry development, new contribution will be made to Chinese health industry by excellent working achievements amenable to the history.