Three points of view in the reform of chemical drug registration and classification

Source: Xinkangjie November 6, 2015, in order to implement the opinions of the State Council on the reform of the review and approval system for pharmaceutical medical devices (GF [2015] 44) (No.) proposed to carry out the pilot work of drug listing license holder system and reform the work of drug registration and classification The food and Drug Administration drafted the pilot plan of drug listing license holder system (Draft for comments) and the work plan of chemical drug registration and classification reform (Draft for comments) (reply to the key word "concentration") View the full text of recent documents) The modification opinions shall be fed back to the food and drug administration by email before November 20, 2015 1、 Definition change of chemicals Draft for comment: according to the degree of safety risk of drugs, drugs are divided into two categories: new drugs and generic drugs; secondly, new drugs are further divided into innovative drugs and improved new drugs according to the difference between the originality and novelty of drugs; thirdly, in generic drugs, according to the different market conditions of the generic drugs, the generic drugs are further subdivided into overseas listed and domestic unlisted drugs to imitate the environment There are three types of drugs to be imitated on the domestic market and drugs to be listed on the overseas market to apply for listing on the domestic market New drugs refer to drugs that are not listed and sold in China or abroad, and drugs that are not listed in China or abroad are included in generic drugs Measures for the administration of drug registration (2007): drug registration applications include new drug applications, generic drug applications, imported drug applications and their supplementary applications and re registration applications The term "application for new drugs" refers to the application for registration of drugs that have not been marketed in China The registration of drugs that have changed the dosage form, changed the way of administration and added new indications shall be declared in accordance with the procedure of new drug application Generic drug application refers to the registration application for the production of national standard drugs approved by the State Food and Drug Administration for listing 2、 In terms of chemical classification and change of chemical classification during new drug monitoring period, "2.5 new dosage and new specifications of preparations containing known active ingredients" have been added In terms of new drug monitoring period, category 2.4 "preparations with new indications of known active ingredients" has no new drug monitoring period in the past The new drug monitoring period for the draft for comments is 3 years, and the new category 2.5 "preparations with new usage, dosage and specifications of known active ingredients" is also 3 years In the administrative measures for drug registration of 2007 edition, there is a corresponding new drug monitoring period for chemical drugs in categories 3.1, 3.2 and 3.3 However, there is no new drug monitoring period after being incorporated into the new three categories of "imitation of drugs listed overseas and unlisted in China" according to the draft for comments The exclusive period of the first generic drug is not mentioned in the draft for classification 3、 Pay more attention to technology in the application materials of new registration and classification of chemicals No matter it is an innovative drug or a releasing drug, the application materials of new registration classification of chemical drugs have clear requirements for production process, process control, material control, key steps and intermediate control The application materials need to include detailed research data, experimental data and atlas, indicating which process steps and quality indicators are optimized and enlarged in the development stage Research, to fully prove that each process has sufficient experimental data support, to ensure that the existing research and production scale, material control, operation process and main equipment are basically consistent with the mass production, the number of batches produced and the quality of each batch of products can reflect a certain degree of reproducibility of the process, and then prove the rationality of the application process and the feasibility of mass production The detailed description of the production process shall enable the technical personnel of the discipline to completely repeat the production process according to the declared production process, and make products that meet the standards In addition, it is also required to submit the detailed description of the main changes of production process (including the changes of batch, equipment, process parameters and process routes) and relevant supporting verification research data during the process development To sum up, the requirements of application materials are more and more grounded, and what can be produced is the king The application materials also require that the process evaluation be related to the stability test and bioequivalence test results, and that the sample information of representative batches (including but not limited to clinical research batches, pilot batches, production site inspection batches, process validation batches, etc.) in the R & D process be summarized, including batch number, production time and place, batch scale, purpose (such as for stability) Sexual test, for bioequivalence test, etc.), analysis results (such as related substances, dissolution and other main quality indicators) This paper lists and compares the similarities and differences between the prescription process, production equipment, batch, control of key process steps and process parameters, control of intermediates, etc of the clinical trial / be test sample and the proposed production line, explains whether these differences affect the quality of the product, and briefly describes the research situation The application data of chemical pharmacy also includes the application data requirements of auxiliary materials and packaging materials / containers However, this draft has not been published together and is still to be issued by the registration department.