Regulations and Guidelines Should Be Strengthened Urgently for Re-evaluation on Post-marketing Medicines in China

This paper reviewed the situation of regulations and guidelines on post-marketing medicines in the developed countries and in China. The developed countries have accumulated a lot of empirical principles and techniques on post- marketing surveillance （also named pharmacovigilance）, therefore, their regulation systems are nearly perfect. In China, the regulations on post-marketing re-evaluation and relative technical guidelines do not cover the whole aspects, even lack in some important aspects, and long-term risk management mechanisms have not been established. So it is urgent to establish new regulations and improve the regulatory system in China based on the existing regulations and guidelines, by learning from the ideas of foreign advanced regulations, then fully integrating them with China＇s actual conditions, and cooperating with multidisciplinary researchers.

Post-marketing safety monitoring of Shenqifuzheng injection: a solution made of Dangshen(Radix Codonopsis)and Huangqi(Radix Astragali Mongolici)

OBJECTIVE:Toidentify the potential risk factors associated with Shenqifuzheng injection(SFI), a solution made of Dangshen(Radix Codonopsis) and Huangqi(Radix Astragali Mongolici), for the timely provision of information to regulatory authorities.METHODS: A comprehensive analysis of the production process, quality standards, pharmacology,post-marketing clinical studies, and safety evaluation using the primary literature of adverse reactions(ADR), case analyses, and systematic reviews,intensive hospital safety monitoring of post-marketing drugs, and data provided by the hospital in-formationsystem(HIS).RESULTS: Sub-acute toxicity tests suggesting that a dose of 15 mL/kg(concentrated solution) had specific biological effects, whereas a smaller dose engendered no observable effects. Long-term toxicity testing in domestic rabbits showed that after SFI was administered for 90 days, the animals in each dosing group showed no chronic toxic reactions. Among 20 100 cases observed, the incidence of an ADR was 1.85‰. From March to November 2013,of the leading institutions and 22 sub-centers involved in the post-marketing clinical safety intensive hospital monitoring, 21 units completed 8484 cases of monitoring, and reported 23 cases of adverse reactions. No damage to renal function was found using SFI ata dosageanda treatment course larger and longer than that recommended for the adjuvant treatment of tumors. This could reduce the mortality rate of admitted patients based on the analysis of the data provided by the HIS. A total of 16 clinical case reports of adverse reactions related to SFI in 1999-2012 were obtained through literature retrieval. These reports contained information concerning 17 cases, with adverse reaction symptoms including thrombocytopenia, rash,chills,feeling cold,palpitation,dyspnea,edemaofa lower extremity, palpebral edema, and superficial vein in flammation,among others.CONCLUSION: This study introduces "get full access" to the flow of information on medicines regarding their ADR incidence rate and characteristics and factors.It supports the safety of SFI for clinical, research, and production uses based on objec-tive, reliable, and scientific information to provide safe medication.

Bias in multiple-treatments meta-analysis： a case on comparative efficacy and tolerability of 15 antipsychotic drugs for schizophrenia

Multiple-treatments meta-analysis is thought to be a feasible method to compare the efficacy and safety among different treatments, especially when there was no head-to-head research among some treatments. But sometimes some conclusions are inconsistent with the clinical experience. Recently, we read a multiple-treatment meta-analysis finished by Stefen Leucht et al, which was published in Lancet） The authors summarized the results of the RCT studies on 15 antipsychotics commonly used in practice; they also horizontally compared the efficacy and safety profile by the recta-analysis. We believe that the results provide more solid evidence for the rational usage of antipsychotics to the psychiatrists, also for the government to distribute health resources in a more reasonable way.

Brief introduction for application of USA authorized generic drugs

The authorized generic drugs(AGs)are drug products marketed in the USA with the permission of sponsor or holder of the approved brand name drug(usually refers to an innovator drug).Other than the fact that it does not have the brand name on its label,it is the exact same drug product as the brand name product.In China,for those published comparator products of generic drug products,the market availability is the first question to affect the smooth development and investigation for the process of the re-evaluation of the generic drugs.In the present paper,we systemically elaborated the definition,classification and relevant background of the AGs,as well as their differences to the generic drugs.At the same time,by taking drug products,which are adopted in the Chinese comparator product directories for generic medicinal products(first batch)and sourced from USA orange book,as examples,we introduced the searching process of the AGs with the integration of FDA listing of AGs,the USA orange book and the USA national drug code directory.It can facilitate the domestic and foreign pharmaceutical enterprises to search,identify and purchase the corresponding AGs of the designated comparator product when question emerges to its market availability.

Safety and Diagnostic Image Quality of Ultravist^®in an Unselected Sub-Set of Chinese Patients: Data Analyses from a Previous Post Marketing Surveillance

Background: Iopromide (Ultravist&reg) has been shown to be a very safe CM agent in previous post-marketing surveillance studies on Western and Asian populations. Our study aimed to analyse data pertaining to the safety, tolerability and diagnostic image quality of Iopromide in an unselected sub-set of the Chinese population. Methods: we analysed data for Chinese ambulatory and in-patients who received Iopromide for an imaging procedure (in accordance with the local package insert and routine clinical practice), as part of an international post-marketing surveillance study. Use of premedication was at the discretion of the attending physician. Patient demographics, clinical history, type of examination, contrast quality and tolerability, including pre-specified adverse drug reactions, were recorded. All statistical analyses were descriptive. Results: case report forms for 20,000 Chinese patients (61.3% men) were analysed, of whom 153 patients (0.77%) had risk factors for idiosyncratic contrast media reactions (at-risk group). Use of premedication, most commonly corticosteroids, was recorded for 5658 patients (28.3%) and 86 at-risk patients (56.2% of the at-risk group), respectively. The mean (±standard deviation) dose of iodine administered was 29 ± 5.5 g. During the physician’s evaluation of image parameters, contrast quality was considered to be “good” (64.7%) or “excellent” (29.3%) in the majority of patients. 571 patients (2.9%) experienced at least one adverse drug reaction [most frequently nausea (0.70%) and dysgeusia (0.62%)], which were typically transient and of mild intensity. Two serious adverse drug reactions were reported [edema (n = 1), decreased blood pressure and dyspnea (n = 1)]. The incidence of adverse drug reactions was increased in the at-risk group versus the overall patient population, and tended to reduce with premedication (mainly corticosteroids). Conclusions: Iopromide was well tolerated and proved to be an efficient contrast agent in a large, non-selected sub-set of Chinese patients undergoing different types of diagnostic imaging procedures.

ADRs and Children： Knowledge and Methodological Standard in PASS （Post Authorization Safety Studies）

PhV （pharmacovigilance） knowledge has the outcome of being inadequate in particular due to the lack of instruction. Pediatricians have to face the realization that over-the-counter medicines increments the peril of ADRs （adverse drug reactions） has become a public health concern. The purpose of this article is to disseminate knowledge of the PhV and to highlight the cultural and organizational difficulties for its implementation. The objectives of promoting the organization of specific training courses and research projects aimed at： （1） to foster the culture of iatrogenic disease in pediatrics; （2） to improve the appropriateness of prescribing drugs in children; （3） to enco.urage spontaneous reporting of ADRs in children; （4） to involve Pediatricians in PASS （post-authorization safety studies） according to GCP, GVP and ENCEPP Code of Conduct. An up to date proposal of PhV, a procedure of preparation improves the productivity of creating novel informative reports which can be utilized for a benefit/risk scrutiny making strides in medicine prescription. In this context, FP-MCRN （family paediatficians-medicines for children research network） established with the aim of developing competence, infrastructure and education for paediatric clinical trials, plays a crucial role in paediatric PhV, through an improvement of PhV training, a correct research methodology and very strong relationship with the families. The initial necessity is cultural, implementing culture of iatrogenic illnesses and a watchful evaluation of the importance of PASS by FPs （family pediatricians）. Participation in clinical trials that generates a precise database administered by FPs together with follow-up outcomes becomes relevant and vital for a scrupulous and accurate assessment of ADRs. PASS can foresee on one hand training and information regarding the proper use of drugs in children and possible iatrogenic pathologies caused by their improper use, the other to constitute a territorial survey in the prescriptive appropriateness and safety of pediatric drugs aimed at evaluating the risk-benefit balance on usage.

Brief introduction for application of the USA national drug code

The reference listed drug (RLD) adopted in the USA orange book is the important source of the Chinese comparator product directories of generic medicinal products. Therefore, its availability has the vital significanee for pharmaceutical enterprise to carry out the re-evaluation of gen eric medici nal products and study of generic medicinal products. The nati onal drug code (NDC) is the unique, 3-segment number for each drug product in USA, and it serves as a universal product identifier for drugs. While the NDC directory adopts the infbrmation of drug products in the current commercial distribution, including all of the prescription drug and over the counter (OTC) drug products. The composition and configuration of the NDC number are systemically elaborated in this paper, as well as the data source, development history and supporting measures of the NDC directory. At the same time, by taking drugs, which are adopted in the Chinese comparator product directory of generic medicinal product (first batch) and sourced from USA orange book, as example, it introduces the application of the NDC directory in the availability aspect of the Chinese comparator products to facilitate the Chinese or foreign pharmaceutical manufacturers to search, identify and purchase the suitable RLD sourced from USA orange book. Moreover, it can provide referenee for Chinese drug regulatory to prepare the Chinese comparator product directories of generic medicinal products.