The Agency's introduction of GVP to clarify the responsibility of the main body of drug alert will impact all MAH

Drug alert refers to the monitoring, identification, evaluation and control of adverse drug reactions and other harmful reactions related to drug use.
From the 2018 Notice of the State Drug Administration on Direct Reporting of Adverse Reactions by Drug Market Holders (No. 66 of 2018), to the Notice of the State Drug Administration on guidelines for the Collection and Reporting of Adverse Drug Reactions (No. 131 of 2018), to the enactment of the Drug Administration Act of 2020, there has been reference to drug alerts.
the newly revised Drug Administration Law, for the first time, proposes the establishment of a drug alert system from the perspective of national legislation, which together with the drug traceability system and the drug listing license holder system constitute the basic system of drug management in China.
December 3, the General Division of the State Drug Administration issued the "Drug Alert Quality Management Code" (draft for comments) (GVP), China's drug alert system is about to enter the implementation phase.
This code is a new regulation for China to implement the drug alert system and implement the main responsibility of the holder's drug alert, compared with the previous drug adverse reaction reporting system, the following new requirements are put forward for the holder: (1) Drug alert system construction 2018 No. 66 draws on the concept of the EU drug alert system and drug alert authority (QPPV), puts forward the construction requirements of the drug adverse reaction monitoring system, and requires the holder to be equipped with the person in charge of drug adverse reaction monitoring.
this specification continues this requirement by renaming it the "Drug Alert System" and "Drug Alert Head" and crafting a specific interpretation of what kind of drug alert system the holder has established and what conditions the person in charge of the drug alert is equipped with.
At the same time, drawing on the experience of the European Union, the holder is required to formulate a "main document of the drug alert system" and make a comprehensive description of its warning system, including institutions, personnel, systems, resources, etc., which on the one hand is conducive to the overall planning of the holder's own system construction, on the other hand, it is also convenient for the regulatory authorities to carry out drug alert inspection.
(ii) The scope and time limit of drug adverse reactions reporting For the transformation and implementation of ICH-related guidelines, Bulletin No. 66 of 2018 adjusts the scope and time limit requirements for drug adverse reactions after market.
This Code continues the relevant requirements, and compared with Order 81, the scope of adverse reaction reporting extends from the inherent properties of the drug, i.e. adverse reactions under the normal dosing of qualified drugs, to adverse drug reactions and other harmful reactions, including harmful reactions that may occur in the context of drug quality or over-instruction.
reporting time frame is also largely in agreement with ICH guidelines.
technical requirements for the ICH Guidelines are also reflected in this specification.
(iii) Drug Safety Update Report ICH guidelines require pre-market bidders to submit a "Safety Update Report during Development" (ICHE2F) and post-market holders to submit a "Regular Security Update Report" (ICHE2C-R1) or a "Regular Benefit Risk Assessment Report" (ICHE2C-R2).
July 2020, the State Drug Administration issued the relevant announcements for the application of ICHE2F and E2C-R2, and this Code puts forward requirements for the consistency of the bid and holders with the ICH guidelines.
In addition to submitting a Periodic Security Update Report (PSUR) under Order 81 after listing, holders are required to submit a Periodic Benefit Risk Assessment Report (PBRER), so the risk assessment also transitions from a purely security assessment to a comprehensive benefit risk assessment.
(4) Signal detection and post-market safety research According to the requirements of the Drug Control Law for holders to conduct post-market research, this specification puts forward new requirements for holders to conduct post-market safety research, and clarifies the scope, type, initiation, purpose and method of post-market safety research.
specific technical requirements are only principled and need to be developed at a later stage for more detailed technical guidelines.
risk identification is a key component of drug alert, but also a weak link in China's current regulations and technical guidelines.
signal detection is a means of risk identification.
This Code, in order to improve the ability of risk identification of holders, drawing on the technical requirements of COMS and the experience of the European Union, put forward the concept of signal detection for the first time, and made principled provisions on the frequency, method and related requirements of signal detection, which provided a basis for holders to expand the content of drug alert work, and also laid a foundation for the future introduction of relevant technical guidelines.
(v) Drug alert plan and risk communication Drug control law stipulates that holders should develop a post-market drug risk management plan.
this specification draws on ICH's statement on drug alert plan, and points out that drug alert plan is part of the drug market risk management plan, which includes drug alert plan formulation situation, content requirements, submission requirements, etc.
guidelines for writing guidelines for drug alert plans will need to be developed.
in addition, this code also highlights the requirements of risk communication, clear the object, principles, methods and content of risk communication, drawing on the European Union and the United States put forward a "letter to medical personnel" and "patient safety drug guidelines" new communication methods, and in the light of China's national conditions put forward new requirements.
(vi) To carry out different drug alert activities according to the characteristics of drugs, combined with the reform trend of drug review and approval system reform, put forward new requirements for the monitoring of innovative drugs.
, drawing on the requirements of the European Union on drug alert, put forward the strengthening of the monitoring system, requiring innovative drugs to strengthen the awareness of adverse reaction reporting by marking them in drug descriptions, packaging and labels, according to the characteristics of drug safety.
In addition, in order to reflect the characteristics of Chinese medicine management, it is pointed out that Chinese medicine, ethnic medicine holders should analyze the drug itself (such as toxic composition, etc.), clinical use (e.g. evidence, preparation, preparation, dosage and course of treatment, etc.), the patient's body status and other factors.
(7) drug alert entrustment is similar to drug production, drug alert under the holder system will also produce a commission.
Drug alert itself is a highly technical work, the holder will be part of the drug alert work entrusted (e.g. through commercial channels to collect adverse reactions, through academic institutions to carry out literature search), on the one hand, can save their own human and time costs, on the other hand, is the weak ability of enterprises at this stage to ensure their drug alert level of an effective way.
this code on the commission of drug alert management has been stipulated in principle, in the future may also be with the further development of drug alert constantly updated and raised requirements.
This specification is the first supporting document on drug alert after the revision of the Drug Control Law, which fully follows the principles and requirements of the Drug Control Law in the formulation process, and has the following bright spots: (i) reflects the management concept of the whole life cycle of the drug.
compared with previous drug adverse reaction monitoring work, drug alert includes not only the collection, identification, evaluation and control requirements of adverse reactions after drug market, but also the monitoring and management of adverse drug events during clinical trials.
(ii) adhered to the principle of drug risk management.
drug control law puts forward the principle of risk management in the general rules, and drug alert is the concrete practice of drug risk management.
In the general rules, this Code states that effective drug warning activities should be carried out in the light of the safety characteristics of drug varieties, the risk of drug use should be reduced, and the requirements of drug risk management should be carried out throughout the chapters, from the collection of risk information to the identification, evaluation and control of risks, which is the framework document for holders to carry out drug risk management activities.
(iii) to clarify the main responsibility of drug alert undertakers.
This Code proposes that drug market license holders and clinical trial bidders bear the main responsibility of drug alert according to law, requires holders to establish a drug alert system and carry out quality management, clarifies the key contents and processes of drug alert activities carried out by the holders and bidders, and embodies the concept of dynamic governance and social co-management.
(iv) has planned a blueprint for international development.
In order to meet the international development needs of China's accession to ICH and pharmaceutical industry, this specification draws on the mature drug alert experience in Europe, America and Japan, and adds many new requirements that have been blank or not expressed, such as signal detection, periodic benefit-risk assessment, drug safety research after market, drug risk communication, drug alert plan formulation, etc.
these new regulations provide a guarantee for the pharmaceutical industry to gradually integrate into the development pattern of the global drug alert, and also outline a blueprint for the international development of China's drug alert.
drug alert system for large pharmaceutical companies is relatively perfect, and the overall work can basically meet the requirements of existing laws and regulations.
However, large enterprises usually have a large number of varieties, involving a wide range of adaptation, new drugs and relatively many high-risk varieties and so on, in the discovery of risk signals, how to more proactive implementation of risk management plans, effective control of varieties of risk should be the focus of its next stage of work.
Compared with large pharmaceutical enterprises, medium-sized pharmaceutical enterprises and small enterprises have a relative lack of awareness of drug alert, the establishment of independent full-time institutions is relatively low proportion, full-time staff in terms of both quantitative and professional background, there are disadvantages, it is difficult to ensure the effective development of drug alert work.
there is still a gap between the drug alert system, drug safety monitoring and legal and regulatory requirements of such enterprises, as the risk management of the second half of the drug alert work is even weak, which may make it in the drug alert system after the formal implementation of a greater impact.
Under the general trend of encouraging innovative research and development, innovative pharmaceutical companies should pay more attention to safety research, actively strengthen the continuous monitoring of safety throughout the life cycle of drugs, so as to continuously collect, summarize and analyze, identify important identified risks, potential risks and missing information, timely feedback and effective safety information, and ensure the effectiveness and safety of drugs.
, a higher level of drug alert system is established to enhance the level and ability of drug alert work of China's pharmaceutical production enterprises.
higher requirements for MAH's drug alert level and professional competence.
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