Challenges posed to the European pharmaceutical regulatory system by highly personalized medicines

The European pharmaceutical regulatory system has not yet been challenged by issues related to highly personalized medicines such as those to be found with active substances that affect RNA biochemistry. We review the current status of RNA-based pharmacology and present three possible case histories. The implications for the European pharmaceutical regulatory system are discussed.     

Some Preformulation Studies of Pyruvic Acid and Other α-Keto Carboxylic Acids in Aqueous Solution: Pharmaceutical Formulation Implications for These Peroxide Scavengers

The purpose of this study is to assess some of the variables determining the aldol-like condensation of pyruvic acid (1), a peroxide scavenger, in aqueous solution to parapyruvic acid and higher oligomers. Its stability is compared to 3 other α-keto carboxylic acids, 2 with sterically hindered methylene groups alpha to the keto functionality (2-3) and phenylglyoxylic acid (4) with no methylene group. High-performance liquid chromatography, nuclear magnetic resonance, and liquid chromatography mass spectroscopy techniques are used in the kinetics and product analyses. 1 condensation is concentration dependent and base catalyzed above pH 7, consistent with the reaction mechanism proceeding through the attack of the fraction of the methylene group, alpha to the keto group, in its anionic form, at the keto group of a second molecule of 1. The major product is confirmed to be parapyruvic acid, but higher-order oligomers are also observed. All 3 of the other α-keto carboxylic acids 2-4 are considerably less reactive, with 4 being completely stable. Stable solutions of 1 can be prepared by the use of relatively dilute solutions maintained at slightly acidic pH values. 1 prevents the oxidation of methionine on addition of hydrogen peroxide.     

Design and Evaluation of a Self-Care Educational Activity as a Student Learning Experience

Objective. To design an educational activity and evaluate its effectiveness on increasing third-year pharmacy students’ knowledge and confidence to recommend self-care products to patients.Design. Faculty members created a self-care activity, the Amazing Self-Care Race, for educational use in a pharmaceutical care laboratory course. Student teams worked competitively to complete 15 stations focused on self-care. A complex, real-world case was presented at each station. Student recommendations were presented to a facilitator. Prior to and following the activity, students were invited to complete an online anonymous survey instrument.Assessment. Eighty-six students completed presurvey and postsurvey instruments to assess their knowledge and perceived confidence to recommend a self-care product to a patient prior to and following participation in the Amazing Self-Care Race. Students demonstrated a significant increase in their ability and confidence to recommend self-care products following the activity (p<0.001).Conclusion. The Amazing Self-Care Race is an effective educational activity that increases student knowledge and confidence in self-care therapeutics. The activity helped students to develop self-care skills, enabled them to learn through doing, encouraged them to synthesize information while making self-care recommendations, and helped them to develop confidence by thinking on their feet.     

江苏省医药上市公司资本配置效率分析

本文对江苏省医药上市公司资本配置效率进行了实证分析，并将江苏省医药上市公司与浙江省、上海市等长三角地区的医药上市公司进行了比较研究，分析江苏省医药上市公司与其它地区资本配置存在的差异，并在此基础上提出优化企业资本配置效率的建议。     

Chemical and biological properties of polymer-modified proteins

Modification with polymers such as polyethylene glycol (PEG) can increase circulating lifetime, reduce immunogenicity and simplify the handling of pharmaceutical proteins. These benefits are currently exploited in six marketed polymer-modified protein therapeutics and about a dozen product candidates in clinical trials. However, traditional protein modification techniques are restricted by the limited control over polymer structure and the location and number of polymer attachment sites. New technology, in the form of chemical protein synthesis and the generation of precision polymers, has been applied to generate synthetic erythropoiesis protein (SEP). This promising treatment for anaemia has been synthesised with precision polymer modification methodology to improve the target protein pharmaceutical. The chemical and biological properties of proteins prepared by both traditional and novel approaches are contrasted in this discussion of chemical protein synthesis and polymer modification in protein drug discovery.     

A proposal for a drug product Manufacturing Classification System (MCS) for oral solid dosage forms

Abstract

This paper proposes the development of a drug product Manufacturing Classification System (MCS) based on processing route. It summarizes conclusions from a dedicated APS conference and subsequent discussion within APS focus groups and the MCS working party. The MCS is intended as a tool for pharmaceutical scientists to rank the feasibility of different processing routes for the manufacture of oral solid dosage forms, based on selected properties of the API and the needs of the formulation. It has many applications in pharmaceutical development, in particular, it will provide a common understanding of risk by defining what the “right particles” are, enable the selection of the best process, and aid subsequent transfer to manufacturing. The ultimate aim is one of prediction of product developability and processability based upon previous experience.

This paper is intended to stimulate contribution from a broad range of stakeholders to develop the MCS concept further and apply it to practice. In particular, opinions are sought on what API properties are important when selecting or modifying materials to enable an efficient and robust pharmaceutical manufacturing process. Feedback can be given by replying to our dedicated e-mail address (mcs@apsgb.org); completing the survey on our LinkedIn site; or by attending one of our planned conference roundtable sessions.     

WHO药品预认证微生物实验室质量管理的要求与思考

目的:介绍世界卫生组织(WHO)对药品微生物检测实验室的预认证要求,推动我国药品检测质量管理体系的完善和发展。方法:从预认证实验室应遵循的质量管理原则出发,对照我国实验室ISO/IEC 17025体系要求,分析药品微生物检测实验室在质量管理中的不足。结果:预认证实验室更多地采纳了《药品生产质量管理规范》(GMP)的质量管理理念,而我国药品微生物检测实验室在记录与数据可靠性、基于风险的变更控制和偏差调查等方面的应用与实施还存在较大差距。结论:我国药品微生物检测实验室应学习和借鉴国内外GMP的质量管理经验,不断更新理念,改进质量管理体系,更多地以风险评估方式保障检测数据的可靠性。     

Liquid Oil Marbles: Increasing the Bioavailability of Poorly Water-Soluble Drugs

Many new therapeutic candidates and active pharmaceutical ingredients (APIs) are poorly soluble in an aqueous environment, resulting in their reduced bioavailability. A promising way of enhancing the release of an API and, thus, its bioavailability seems to be the use of liquid oil marbles (LOMs). An LOM system behaves as a solid form but consists of an oil droplet in which an already dissolved API is encapsulated by a powder. This study aims to optimize the oil/powder combination for the development of such systems. LOMs were successfully prepared for 15 oil/powder combinations, and the following properties were investigated: particle mass fraction, dissolution time, and mechanical stability. Furthermore, the release of API from both LOMs and LOMs encapsulated into gelatine capsules was studied.