Quality consistency evaluation of generic drugs will be promoted immediately

Source: new progress has been made in the quality consistency evaluation of generic drugs on February 17, 2014 in pharmaceutical economic news Recently, the evaluation methods of metoprolol tartrate tablets, ambroxol hydrochloride tablets and terazosin hydrochloride tablets, as well as the draft technical guidelines of determination and comparison of dissolution curve of common oral solid preparations and establishment principles of reference preparations of oral solid preparations, have been published for comments "At present, the products to be evaluated are all very fast release products Even if the dissolution curves of the existing products are inconsistent, the consistency can be achieved with a little prescription adjustment or process modification." In the interview, a pharmaceutical expert who has long paid attention to the quality consistency evaluation of generic drugs said that he is most concerned about five categories of preparations, including insoluble drug preparations, enteric preparations, slow and controlled release preparations, pH dependent preparations, which are difficult and need most attention If we want to improve the quality of the preparation, the relevant enterprises should carry out in-depth research on the factors that determine the quality of the preparation For the varieties with difficulties, it is suggested that the enterprises that want to keep the document number should carry out "secondary development" in advance We have learned from the interviews with reporters that the industry is particularly concerned about the detailed provisions of the above guidelines and the determination of the follow-up reference preparations Enterprises are also actively carrying out the quality consistency evaluation of generic drugs, and some are actively competing for the reference preparation Enterprises that are willing to provide reference preparations apply to CCID, which is also mentioned in the draft However, some business people are worried about how to balance the selection of reference preparations According to the above experts, at present, the application and selection system is adopted to establish the reference preparation, which should be adopted by the management department in full consideration of the current particularity and complexity of China's pharmaceutical industry Compared with the international practice, this is a new thing and requires concerted efforts However, he also reminded that the declaration of reference preparation is a double-edged sword: the benefits obtained after being selected as reference preparation are self-evident, after all, it is closely related to the market competition game At the same time, it will also become the focus of attention Competitors of the same kind will continue to purchase the reference preparations for marketing and test their key indicators for comparative analysis If their quality is not strong, they will be reported until they are removed and replaced, which is very embarrassing Therefore, it is suggested that relevant laws and regulations such as quality supervision system and replacement system of reference preparation should also be formulated, which also needs rational response of enterprises On the other hand, according to the feedback from the enterprise, the expert believes that there are the following main policies to be formulated urgently: first, make clear as soon as possible the degree of "secondary development" required by the quality consistency evaluation of generic drugs, whether it is in accordance with the general requirements of generic drug R & D application or appropriate compromise Second, for the products that are inconsistent with the dissolution curve of the reference preparation, it is necessary to make clear how long the "secondary development" will be given to the enterprise Is the door of consistency evaluation always open, or how long will it be closed? The time limit is closely related to the above technical requirements Third, there will be a large number of supplementary applications in the evaluation process Because the enterprise's preparation research needs to be improved and even overturned, how can the supplementary application ensure the timely completion of the review? At present, there are a large number of pending varieties waiting in line in the drug audit center Fourth, some necessary imported auxiliary materials used may not have import registration certificate at present, can they be used? All of these need to be matched with corresponding specific regulations as soon as possible, so that enterprises can carry out the consistency evaluation research with a targeted goal These suggestions aroused the resonance of Xu Qiang, vice president of Furen Pharmaceutical Group He said that the company has more than 80 consistency evaluation projects involving solid preparations At present, the evaluation work has just started, and most of them are in the stage of comprehensive research and development "The most distressing thing now is that it will take a lot of resources and time to go according to the supplementary application." Xu Qiang suggested that a green channel should be set up for this purpose At present, some pharmaceutical enterprises have completed the research of related varieties and submitted supplementary applications for basic research The evaluation methods of the other 13 varieties in the first batch will be published one after another and gradually pushed forward In addition to simple varieties, pharmaceutical companies are also worried about relevant research There are 16000 kinds of drugs approved for marketing in China, most of which are generic drugs In recent years, the relevant departments have carried out evaluation sampling tests on many kinds of drugs, and found that many dissolution curves of many marketed preparations in vitro are quite different from those of the original preparations Xu Qiang said frankly that as a large-scale base drug production base in China, the company selected the varieties for evaluation based on the company's sufficient R & D strength, large sales of single products, focusing on enteric coated preparations, sustained-release and controlled-release preparations, insoluble drugs and other fields "The main difficulty at present is that there is a big gap between the domestic R & D strength and the original research drug, especially the research on the characteristics of raw and auxiliary materials The domestic raw materials differ greatly from batch to batch, and the reproducibility is not good Even in the same prescription process, the curves of raw and auxiliary materials of different batches are not the same at last, and the cost of using foreign raw and auxiliary materials is high." The reporter learned that Shenyang ojina Pharmaceutical Co., Ltd is the first to imitate 100mg aspirin enteric coated tablets in China, and the test proved that it has bioequivalence with the original research drug Bayaspirin But Wei Guoping, chairman of the company, said, "in general, the theoretical and practical ability of Chinese pharmaceutical engineers needs to be improved." The high technology of pharmaceutical industry lies in pharmacy and industrial pharmacy In the interview, the aforementioned experts suggested that preparation enterprises must conduct in-depth study on the factors such as raw and auxiliary material characteristics, preparation process, production equipment, personnel and technical level that determine the quality of preparations Only when the characteristic parameters of these factors are verified and the fluctuation range of process parameters of industrial production is determined, can the dissolution curve of the preparation be consistent with that of the original preparation, and the quality of the product within and between batches be ensured to be uniform and constant Whether these elements can be controlled accurately and correctly, to a large extent, can be expressed acutely and sensitively through multiple dissolution curves in vitro It is reported that at present, the research of the prazole enteric preparation and other varieties is still relatively weak An executive of a pharmaceutical company in Shenzhen, who did not want to be named, told reporters that in addition to the research on technology, it is more important to identify suppliers and do a good job in auditing suppliers themselves "The energy of the enterprise is now focused on dealing with the differences in approval documents caused by different raw and auxiliary materials, but not on the prescription process." He suggested that strict process verification should be carried out for APIs, and the most urgent thing for excipients is to establish normative certification, which is a problem in the industrial chain At the same time, it is also necessary to coordinate the promotion of policy level, introduce incentive measures in bidding procurement, pricing and medical insurance reimbursement, and guide enterprises to actively improve the quality.