Generic drugs are alternative drugs with the same active ingredients, dosage forms, routes of administration and therapeutic effects as generic drugs, and have important economic and social benefits such as reducing medical expenses, improving drug accessibility, and improving medical service levels. Due to the relatively weak foundation of early-approved generic pharmaceutical research, the quality of some generic drugs is far from that of generic drugs, and the clinical efficacy of generic drugs cannot be achieved. Improving the quality of generic drugs is of great significance for maintaining public health. The National Twelfth Five-Year Plan for Drug Safety clearly stated that it will take 5 to 10 years to conduct a comprehensive comparison study on generic drugs before the implementation of the revised Drug Registration Regulations in 2007. To make the generic drug consistent with the generic drug. In order to implement the relevant requirements of the National Twelfth Five-Year Plan for Drug Safety, this work plan has been formulated.
I. Work Objectives The quality consistency assessment of generic drugs is organized by the State Food and Drug Administration to organize relevant technical departments and experts. The self-assessment data of generic drugs proposed by pharmaceutical manufacturers shall be evaluated according to the given evaluation methods and standards. Generic drugs have a consistent process of intrinsic material and clinical efficacy. Through the consistency evaluation of generic drugs, it is necessary to eliminate the varieties whose internal quality is not up to the requirements, and promote the overall level of generic drugs in China to reach or approach the international advanced level.
Second, the working method
(1) Piloting first, then pushing forward, and gradually advancing. Select the basic drug list, the market share is large, the market sales are large, the production enterprises are many, and the varieties of the original research enterprises are tested first, the experience is accumulated, and then gradually pushed forward, comprehensively promoted, and gradually improve the quality evaluation system of generic drugs, and build the quality of drugs. Improved working mechanism.
(2) Classification and processing by scientific and reasonable technical methods. Based on the principle of scientific rationality and classification, the quality consistency evaluation of generic drugs is combined with the improvement of drug standards and evaluation work, and is carried out step by step according to the nature of the drug and the characteristics of the drug dosage form. First, the consistency evaluation of oral solid preparations was carried out; secondly, the consistency evaluation of injections was carried out; finally, the consistency evaluation of other dosage forms was carried out.
Third, job responsibilities
(1) The State Food and Drug Administration is responsible for the organization and implementation of the evaluation of the quality consistency of generic drugs. Organize the development of a generic drug quality consistency evaluation work program, issue relevant evaluation methods, standards and technical guidelines, and organize the review of the conformity evaluation materials submitted by pharmaceutical manufacturers. The State Food and Drug Administration will set up a special office to be specifically responsible for this work.
(2) The provincial drug supervision and administration department is responsible for the organization and coordination of the evaluation of the quality consistency of generic drugs within its jurisdiction. To undertake the implementation and publicity of the quality consistency evaluation of generic drugs, and urge the drug inspection agencies within the jurisdiction to complete the tasks undertaken on time, in accordance with the consistency evaluation work deployment and cooperate with relevant training, and accept the acceptance and production of the conformity evaluation materials according to the requirements. On-site inspection and sampling inspection.
(3) The pharmaceutical production enterprise is the main body for the evaluation of the quality consistency of generic drugs. In accordance with the unified deployment of the State Food and Drug Administration, in accordance with relevant technical guidelines, evaluation methods and standards, comprehensive and in-depth comparative research with generic drugs should be carried out to solve the key problems affecting the intrinsic quality of generic drugs, and to achieve Consistent in terms of intrinsic material and clinical efficacy.
The reference preparation manufacturer shall, in accordance with the requirements of the State Food and Drug Administration, cooperate with the drafting of evaluation methods and standards, as well as the supply of reference preparations.
Fourth, the work content
The quality consistency evaluation of generic drugs is mainly for basic drugs and common chemical drugs in clinical practice. The main work includes: selecting the varieties to be evaluated, determining the reference preparations and establishing evaluation indicators, self-evaluation of the enterprises, and reviewing the self-evaluation materials of the drug regulatory authorities. Steps (see the attached work flow chart).
(1) Determining the category to be evaluated The special office shall formulate an annual work plan, determine the list of varieties for annual quality consistency evaluation, and the drug inspection agency responsible for the research work of each variety evaluation method, and publish it. In the early pilot varieties, it was confirmed that the drugs of the original research institutes were first explored.
(2) Determining the reference preparation and related detection and analysis methods
1. The special office organizes the drug inspection agency and the reference preparation manufacturer, and formulates the quality consistency evaluation methods and standards for each variety according to the “Procedures and Requirements for Reference Preparation” and the “Technical Guidelines for the Evaluation of Drug Quality Consistency”. Solicit opinions from relevant pharmaceutical manufacturers.
2. The special office organizes experts of relevant drug inspection agencies and technical experts of relevant pharmaceutical production enterprises to improve the quality consistency evaluation methods and standards of each variety according to the opinions of the solicitation.
3. The reference preparation manufacturer shall prepare the reference preparation according to the requirements, and the drug inspection agency shall conduct a quality review of the reference preparation and submit the result to the special office.
4. The State Food and Drug Administration shall review the various reference preparations and quality consistency evaluation methods and standards submitted by the special office, and if they meet the requirements, they shall be announced.
(III) Research on the quality consistency evaluation of pharmaceutical production enterprises All relevant pharmaceutical production enterprises carry out the evaluation of the quality consistency of generic drugs in accordance with the evaluation methods and standards promulgated by the State Food and Drug Administration and the reference preparations as the control drugs. After the enterprise completes the assessment, the research materials and samples will be reported to the provincial drug regulatory authority.
If it is necessary to change the prescription, process, etc., the relevant change research materials (see the Drug Registration Management Measures) and the conformity evaluation research materials may be reported to the provincial bureau.
(4) Acceptance and on-site inspection of generic drug quality consistency evaluation data
After receiving the research materials of the pharmaceutical production enterprise, the provincial drug supervision and management department shall organize the production site inspection according to the approved or declared process, and extract 3 batches of samples for continuous production on site, and send the drug inspection agency responsible for the quality consistency evaluation of the variety. Conduct a review check. After receiving the samples, the drug inspection agency shall review the methods and standards promulgated by the State Food and Drug Administration, and report the results of the review to the relevant provincial drug regulatory authorities.
After receiving the results of the review by the drug inspection institute, the provincial drug supervision and administration department will report the research materials and inspection reports to the special office.
(V) Review of generic drug quality consistency evaluation data
After receiving the consistency evaluation research materials, the special office shall organize an expert committee to review the research materials submitted by the enterprise. If the examination meets the requirements, the special office shall report to the State Food and Drug Administration for approval, and the State Food and Drug Administration shall publish relevant information (name of production enterprise, name of drug, approval number, etc.).
If the examination does not meet the requirements, the special office will inform the pharmaceutical production enterprise.
Any changes to the prescriptions and processes shall be reviewed by the special office organization experts, together with the results of the quality consistency evaluation review and reported to the State Food and Drug Administration, and the State Food and Drug Administration shall issue the “Approval for Drug Supplementation”.
Pharmaceutical manufacturers may also carry out research work on the quality assessment of the national bureaus that have not yet been deployed according to their needs. After completing the drafting of evaluation methods and standards, they will report to the special office. The special office organized the drug testing institute and experts to review the evaluation methods and standards drafted by the pharmaceutical production enterprises, and then publicize them to initiate the consistency evaluation of the relevant varieties.
V. Work plan
(1) In 2012, carry out variety research work, introduce relevant guidelines for quality consistency evaluation of oral solid preparations, and initiate screening and evaluation of reference preparations.
(II) In 2013, establish a catalogue of reference preparations; build a database of oral solid preparation generic drugs, establish an information transmission system between national bureaus, drug inspection agencies and enterprises; complete the selection and confirmation of reference preparations.
(3) In 2014, comprehensively carry out comparative research and evaluation of oral solid preparations and reference preparations. Improve the construction of information systems and complete the evaluation of the quality consistency of some varieties.
(IV) In 2015, complete the task of quality consistency evaluation of solid oral preparations in the essential medicines catalogue.
(5) From 2015 to 2020, carry out quality consistency evaluation of injections and other dosage forms.
Sixth, work security
(1) Establishing a leading group and supervision team for the evaluation of the quality of generic drugs. Responsible for the organization of leadership, overall coordination and external publicity work, review the work plan, study and solve major problems in the work, guide and supervise the implementation of various tasks. The leading group has a special office, which is located at the China Food and Drug Control Research Institute, and is responsible for the specific implementation of generic drug quality consistency evaluation.
Established a quality inspection evaluation team for generic drugs. Mainly perform supervisory duties and ensure that the consistency assessment work is objective, fair and fair.
(2) Establishing relevant committees and technical working groups. Established a generic drug quality consistency evaluation technical working group, mainly responsible for the technical guidelines for the evaluation of generic drug quality consistency, and the validation of relevant methodologies; established a review committee for generic drug quality consistency evaluation, responsible for the consistency of generic drug quality Evaluation of evaluation data, responsible for the check of major technical issues.
(3) Establish a special information management platform. Establish an electronic information column for the evaluation of generic drug quality consistency, publish generic drug evaluation programs, technical guidelines and variety information through generic drug evaluation, and guide and standardize enterprises to conduct research. It is necessary to make full use of information technology, improve internal management, optimize management processes, and ensure the openness and transparency of quality consistency evaluation.
(4) Strengthen the management of archives. In accordance with the relevant requirements of the national archives management, the work archives of the quality consistency evaluation of generic drugs should be well preserved and managed to ensure the completeness and traceability of the document materials.
(5) Do a good job in fund use. Each task undertaker shall, in accordance with the relevant provisions of the fund management, set up special accounts and personnel to strengthen the management of work funds and ensure the safe and efficient use of funds.
(6) Strict work discipline. All relevant units must select personnel with high political quality and strong business ability to participate in the evaluation of the quality consistency of generic drugs. It is necessary to strengthen the business training and integrity, confidential education, uniform standards, strict standards, and strict work discipline for the participants to ensure that the consistency evaluation work is fair and just.
Attachment: Flow chart of generic drug quality consistency evaluation Drafting of work plan for generic drug quality consistency evaluation (Drug Registration Division November 2012)
I. Drafting Background At present, China has approved 16,000 kinds of drugs for listing, and the number of drug approvals is 187,000. Among them, there are 0.7 million kinds of chemicals, and the approval number is 121,000. Most of them are generic drugs. On the whole, the development of generic drugs in China has made great progress, effectively solving the outstanding problems of the people lacking medical care and medicine, and playing an important role in maintaining public health. With the in-depth development of medical reform work and the gradual improvement of the public's living standards, the requirements for the quality of medicines are increasing. The potential problems of generic drugs in China are also becoming more and more prominent. Some of the quality of generic drugs is far from the gap between generic drugs. To a certain extent, it affects the clinical efficacy of generic drugs and even affects the safety of public medication. In order to implement the task deployment of improving the quality of generic drugs in the National Drug Safety Twelfth Five-Year Plan, and comprehensively improve the quality level of generic drugs, the Work Plan for the Evaluation of the Quality of Generic Drugs (hereinafter referred to as the “Work Plan”) was specially formulated. It is proposed to adopt the Work Plan, propose work objectives, clarify work methods, determine work content and requirements, implement work tasks and responsibilities, ensure orderly and rational development of generic drug quality consistency evaluation, promote overall improvement of generic drug quality, and promote medicine. Healthy development of the industry.
Second, drafting principles
(1) Guided by the scientific concept of development, in accordance with the requirements of the scientific supervision concept, fully consider the development status of China's pharmaceutical industry and the demand for public drugs, and improve the quality of generic drugs in China through reasonable and feasible evaluation methods and standards to ensure the safety of public drugs. .
(2) On the basis of clarifying the overall work objectives, comprehensively plan the quality consistency evaluation work, clarify the working time and content, and advance the quality consistency evaluation work in accordance with the principle of priority.
Third, the drafting process for the implementation of the "National Drug Safety Twelfth Five-Year Plan" deployment tasks, in accordance with the "Notice on the issuance of the national drug safety "Twelfth Five-Year Plan" task division plan (National Food and Drug Administration  No. 40), our company started the drafting of the Work Plan from the beginning of the year. In order to ensure that the Work Plan is scientific, reasonable and operational, our company will go to Japan to understand Japan's experience in quality consistency evaluation and 7 times to solicit opinions from domestic and foreign enterprises, industry associations and experts. Many studies have formed the first draft of the Work Plan. During the period, according to the spirit of the five-time office of Wu Wei, the deputy director of the office was perfected, and the opinions of the political and legal, security supervision, inspection, the Chinese procuratorate, the pharmacopoeia committee, the drug examination center and other departments were sought, and the "work plan" (draft for comments) was finally formed.
IV. Main Contents The Work Plan is divided into six parts. The main contents are as follows: The first part is the “work target”. The definition of generic drug quality consistency evaluation was clarified, and the overall goal of the work was put forward.
The second part is "Working methods." The working methods and strategies adopted for consistency evaluation are proposed. First, piloting and post-promotion will help to timely correct problems that may exist in the work. Second, rational classification, orderly development, and strong public response and mature experience. Oral solid preparations can be followed and then evaluated for other dosage forms.
The third part is "work responsibilities". The responsibilities and obligations of the national bureau, the provincial bureau, and the pharmaceutical production enterprise in the quality consistency evaluation work were clarified. In particular, it is clear that the pharmaceutical production enterprise is the main body of the consistency evaluation work, which is conducive to raising the sense of responsibility of pharmaceutical production enterprises.
The fourth part "work content". The content of the consistency evaluation work and related steps are clarified. The main process and content are: the National Bureau announces the proposed evaluation of the variety and determines the evaluation methods, standards and corresponding reference preparations → → the enterprise uses the reference preparation as the control, evaluates the products according to the evaluation methods and standards, and forms the assessment data to the local provincial bureau. →→The provincial bureau conducts on-site inspection of the enterprise and samples are sent to the drug inspection institute for inspection. The enterprise assessment data, on-site inspection report and sample inspection report are reported to the special office of the national bureau →→ special office organizes the expert for review, which meets the requirements and is announced. The information, if it does not meet the requirements, is returned to the enterprise for re-study.
The fifth part of the "work plan." The work objectives for each year are clarified.
The sixth part is "Work Security." Relevant requirements were put forward from the aspects of organization, personnel, funding, informationization, and archives.
V. Some questions that need to be explained
1. About step-by-step evaluation According to the preliminary work ideas, the evaluation of oral solid preparations will be carried out first. There are three reasons. One is that in the basic drugs, the number of oral solid preparations is the largest, and the clinical efficacy is inconsistent.