下一代风险评估在化妆品原料安全性评价的应用研究进展

下一代风险评估(Next Generation Risk Assessment,NGRA)是在传统的风险评估基础上发展出的一套以暴露为导向、以假设为驱动的新式风险评估框架体系。随着科学技术的发展、3R原则的推广,化妆品安全性评价和风险评估方法也在不断进步。国外已有一些采用NGRA开展化妆品原料风险评估的探索性案例研究,这些案例分析展示了NGRA的评估过程,有助于提高对NGRA原则的理解。文章通过对国际化妆品监管合作组织(ICCR)提出的NGRA原则、框架体系、评估工具以及国外应用NGRA开展化妆品原料安全性评价的案例分析等内容进行系统性的梳理和介绍,提出我国化妆品原料安全性评价面临的挑战,希望为提高我国化妆品技术支撑能力提供研究思路和技术储备。

Defense Against Software-Defined Network Topology Poisoning Attacks

Software-Defined Network(SDN)represents a new network paradigm.Unlike conventional networks,SDNs separate control planes and data planes.The function of a data plane is enabled using switches,whereas that of a control plane is facilitated by a controller.The controller learns network topologies and makes traffic forwarding decisions.However,some serious vulnerabilities are gradually exposed in the topology management services of current SDN controller designs.These vulnerabilities mainly exist in host tracking and link discovery services.Attackers can exploit these weak points to poison the network topology information in SDN controllers.In this study,a novel solution is proposed to defend against topology poisoning attacks.By analyzing the existing topology attack principles and threat models,this work constructs legal conditions for host migration to detect host hijacking attacks.The checking of the Link Layer Discovery Protocol(LLDP)source and integrity is designed to defend against link fabrication attacks.A relay-type link fabrication attack detection method based on entropy is also designed.Results show that the proposed solution can effectively detect existing topological attacks and provide complete and comprehensive topological security protection.

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.

Bridging the structure gap between pellets in artificial dissolution media and in gastro-intestinal tract in rats

Changes in structure of oral solid dosage forms(OSDF) elementally determine the drug release and its therapeutic effects.In this research,synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3 D structure of enteric coated pellets recovered from the gastrointestinal tract of rats.The structures of pellets in solid state and in vitro compendium media were measured.Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media.Thus,optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media.The sphericity,pellet volume,pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for2 h were recorded 0.47,1.55 × 10^(8)μm^(3),0.44 × 10^(8)μm^(3)and 27.6%,respectively.After adding pepsin and glass microspheres,the above parameters in vitro reached to 0.44,1.64 × 10^(8)μm^(3)0.38 × 10^(8)μm^(3)and 23.0%,respectively.Omeprazole magnesium pellets behaved similarly.The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3 D structures to ensure better design,characterization and quality control of advanced OSDF.

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.

The introduction of therapeutic equivalence evaluation codes and its influence on the selection of the reference listed drugs in China

The Approved Drug Products with Therapeutic Equivalence Evaluations(commonly known as the Orange Book)includes the products approved by Food and Drug Administration(FDA)to be marketed in the USA,and it is an essential source for the selection of suitable reference listed drugs(RLD)for a chemical generic medicinal product.The Orange Book assigns a therapeutic equivalence(TE)evaluation code for approved multisource prescription drug products to serve as public information in the area of medicinal product selection.In the present study,we introduced the TE coding system and its influence on the selection of the RLD in China by taking the Topiramate Extended-release Capsules as an example.As a result,it was suggested to determine its TE evaluation code in the Orange Book previously when we choose an RLD and select suitable RLD the first letter of whose TE evaluation code is A to carry out the research and development of a generic medicinal product,which can improve the probability of success of clinical bioequivalence(BE)test and reduce the risk of generic medicinal product development.

Brief introduction for search and determination of the comparator product for generic medicinal product application in the EU

It is vital segment to choose the right comparator product during the development and study of generic medicinal product, and this is also definitely specified in the relevant documents from the China Food and Drug Administration (CFDA)that the comparator product should be innovator product or internationally recognized same medicinal product,which is used in the re-evaluation of generic medicinal product or marketed authorization application of the generic medicinal product.To facilitate the domestic and foreign pharmaceutical enterprises to choose and determine comparator product,four medicinal product evaluation procedures,as well as the corresponding marketed medicinal product list,are detailed elaborated in this paper.At the same time, by taking the Mifepristone Tablet (200mg)as example,the search and determination process of the comparator product for generic medicinal product application in the EU is illustrated with the combination of different marketed medicinal product lists.