• 한국임상약학회지
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• 제28권2호
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• pp.146-153
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• 2018

Objective: Multi-regional clinical trials have been widely used for accelerating global drug development by multinational pharmaceutical companies. In this study, we aimed to review and analyze the international trends in regulations and guidelines on multi-regional clinical trials by regulatory authorities and international organizations, such as International Conference on Harmonisation, for referring to policies, including development of domestic guidelines for multi-regional clinical trials. Methods: The policies, regulations, and guidelines published by the US Food and Drug Administration, European Medicines Agency, Pharmaceuticals and Medical Devices Agency (Japan), and China Food and Drug Administration were searched, and the International Conference on Harmonisation E17 draft guideline was reviewed. Results: The regulatory authorities in developed countries have developed and implemented regulations and guidelines on multi-regional clinical trials to promote simultaneous global drug development and evaluate the regional differences in drug safety and efficacy. International Conference on Harmonisation developed the draft guideline for planning/designing of multi-regional clinical trials in 2016, which recommends the general principles for strategy-related issues and design of multi-regional clinical trials, and for protocol-related issues, such as consideration of regional variability, subject selection, dose selection, endpoints, comparators, overall sample size, allocation to regions, collecting information on efficacy and safety, and statistical analysis. Conclusion: It is important to understand the international regulatory requirements for designing and planning of multi-regional clinical trials for global drug development. Moreover, it is necessary to prepare multi-regional clinical trial guidelines in accordance with the Korean regulation for clinical trials and drug administration.

• 기술혁신연구
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• 제12권2호
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• pp.47-66
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• 2004

The relationship between innovation policies and locational competitiveness has emerged as an important area in the analysis of economic development, reflecting both the centralisation and decentralisation of globalising economic activities. The underlying spatial and institutional components are subject to a pattern of cumulative causation in which strategic interventions of policy actors exercise a decisive role in shaping competitive advantages, while promoting interactions with local and foreign partners both from the private and public sectors. The Singaporean development experience illustrated these strategic interdependencies of innovation policies and locational competitiveness. Based on her role as a manufacturing and service hub, Singapore is viewed as an infrastructural nodal point which is interconnected to global production networks. Paralleling efforts in the domain of technological innovation, Singapore's policies for locational competitiveness aim at an adaptive harmonisation of the needs of international investors with local developmental objectives. This orientation characterises also current efforts in promoting Singapore as a knowledge agglomeration with a distinct science base, expanding R&D operations and an innovation-driven pattern of economic development. In conclusion, the locational rationale of Singapore's innovation policies provides lessons for dealing with the spatial and institutional implications of technological globalisation.

• 한국잡초학회지
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• 제17권1호
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• pp.73-79
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• 1997

Governments and industry have a growing interest in the harmonization of environmental test methods and risk assessment procedures. OECD are currently producing a set of harmonised test guidelines for studying the environmental fate and ecological effects of pesticides. FAO has published an environmental risk assessment procedure. This procedure, which is similar to those used in US and Europe, is based on calculating the ratio of the toxicity of a pesticide to indicator organisms to their level of exposure to the pesticide. The exposure depends on both the concentration of the pesticide and its bioavailability. Ratios which indicate a pesticide will not produce a harmful effect have been established using ecological field studies. Examples are presented for assessing the risk to aquatic ecosystems, earthworms and honeybees. Long-term field studies(up to 20 years) have also shown that pesticides can be used indefinitely without harming soil fertility. Herbicides can be used to avoid the ecologically damaging effects of using soil cultivations excessively for weed control.

• 약학회지
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• 제47권2호
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• pp.104-109
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• 2003

The present paper reviews the notion and comparison of the Korea Food and Drug Administration(KFDA) general pharmacology and the International Conference on Harmonisation (ICH) safety pharmacology. General pharmacology or safety pharmacology is termed the study to determine the potential of a compound to induce adverse pharmacological effects. KFDA general pharmacology studies have been considered an important component in drug safety assessment and these were originally referred to those designed to examine effects other than the primary therapeutics effect of a drug candidate. The KFDA notified the Guideline for General Pharmacology in 1997. Safety pharmacology studies were focused on identifying adverse effects on physiological functions. In the ICH came into place S7A Safety Pharmacology Studies for Human Pharmaceuticals in 2001. A new chemical entity should be assessed for its side effects, initially in those physiological systems which are generally agreed to be the key systems that are essential for life; these "core system" include the central nervous system, cardiovascular system and respiratory system in safety pharmacology studies. These studies should be performed in compliance with Good Laboratory Practice (GLP).

• 대한약침학회지
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• 제17권4호
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• pp.36-49
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• 2014

Objectives: Quercetin and curcuminoids are important bioactive compounds found in many herbs. Previously reported high performance liquid chromatography ultraviolet (HPLC-UV) methods for the detection of quercetin and curcuminoids have several disadvantages, including unsatisfactory separation times and lack of validation according the standard guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Methods: A rapid, specific, reversed phase, HPLC-UV method with an isocratic elution of acetonitrile and 2% v/v acetic acid (40% : 60% v/v) (pH 2.6) at a flow rate of 1.3 mL/minutes, a column temperature of $35^{\circ}C$, and ultraviolet (UV) detection at 370 nm was developed. The method was validated and applied to the quantification of different types of market available Chinese medicine extracts, pills and tablets. Results: The method allowed simultaneous determination of quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin in the concentration ranges of $0.00488-200{\mu}g/mL$, $0.625-320{\mu}g/mL$, $0.07813-320{\mu}g/mL$ and $0.03906-320{\mu}g/mL$, respectively. The limits of detection and quantification, respectively, were 0.00488 and $0.03906{\mu}g/mL$ for quercetin, 0.62500 and $2.50000{\mu}g/mL$ for bisdemethoxycurcumin, 0.07813 and $0.31250{\mu}g/mL$ for demethoxycurcumin, and 0.03906 and $0.07813{\mu}g/mL$ for curcumin. The percent relative intra day standard deviation (% RSD) values were $0.432-0.806{\mu}g/mL$, $0.576-0.723{\mu}g/mL$, $0.635-0.752{\mu}g/mL$ and $0.655-0.732{\mu}g/mL$ for quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively, and those for intra day precision were $0.323-0.968{\mu}g/mL$, $0.805-0.854{\mu}g/mL$, $0.078-0.844{\mu}g/mL$ and $0.275-0.829{\mu}g/mL$, respectively. The intra day accuracies were 99.589%-100.821%, 98.588%-101.084%, 9.289%-100.88%, and 98.292%-101.022% for quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively, and the inter day accuracy were 99.665%-103.06%, 97.669%-103.513%, 99.569%-103.617%, and 97.929%-103.606%, respectively. Conclusion: The method was found to be simple, accurate and precise and is recommended for routine quality control analysis of commercial Chinese medicine products containing the flour flavonoids as their principle components in the extracts.

• 분석과학
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• 제35권3호
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• pp.93-115
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• 2022

의약품의 제조, 유통, 보관 과정에서 발생할 수 있는 잠재적 불순물은 의약품의 품질과 안전에 영향을 미치며 반응성이 높은 불순물의 경우 인체에 대한 발암성(변이원성)을 나타내기도 한다. 이를 위해 국제의약품규제조화위원회(International Conference on Harmonisation, ICH)에서는 "잠재적 발암 위해를 제한하기 위한 의약품 중 DNA 반응성(변이원성) 불순물의 평가 및 관리"에 대한 내용을 담은 M7(R1) 가이드라인을 제공하여 채택을 권고하였다. 하지만 가이드라인에서도 잠재적 불순물에 대한 분류, 섭취 허용량, 관리방안 등과 대표적인 불순물 14 종에 대한 가이드라인 적용을 소개하는데 그치고 있어 제약회사와 규제 당국에서 실제 관리를 위한 의약품 중 잠재적 불순물의 분석에 어려움을 겪고 있다. 이에 따라 본 총설에서는 비의도적 변이원성 불순물의 정의와 ICH M7(R1) 가이드라인에 소개된 내용을 간략하게 살펴보는 한편 현재까지 보고된 주요 잠재적 불순물의 분석 동향을 살펴보고자 한다. 이를 통해 식약처를 비롯한 감독 기관과 제약회사 등에서 의약품 중 잠재적 불순물 관리에 조금이나마 도움이 되고자 한다.

• Bulletin of the Korean Chemical Society
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• 제34권9호
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• pp.2663-2670
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• 2013

The purpose of stability testing is to provide evidence about how the quality of a drug varies with time under the influence of a variety of environmental factors. In this study, erythropoietin (EPO) was analyzed under different pH (pH 3 and pH 9) and temperature ($25^{\circ}C$ and $40^{\circ}C$) conditions according to current Good Manufacturing Practice (cGMP) and International Conference on Harmonisation (ICH) guidelines. The molecular weight difference between intact EPO and deglycosylated EPO was determined by SDS-PAGE, and aggregated forms of EPO under thermal stress and high-pH conditions were investigated by size exclusion chromatography. High pH and high temperature induced increases in dimer and high molecular weight aggregate forms of EPO. UPLC-ESI-TOF-MS was applied to analyze the changed modification sites on EPO. Further, normal-phase high-performance liquid chromatography was performed to identify proposed glycan structures and high pH anion exchange chromatography was carried out to investigate any change in carbohydrate composition. The results demonstrated that there were no changes in modification sites or the glycan structure under severe conditions; however, the number of dimers and aggregates increased at $40^{\circ}C$ and pH 9, respectively.

• Nuclear Engineering and Technology
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• 제56권3호
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• pp.1029-1036
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• 2024

Drawing on the deep experience and understanding of the principles of nuclear safety, as well as many years of nuclear power plant design and operation, the EDF led NUWARD SMR Project is developing a design for a Small Modular Reactor (SMR) of 340 MWe composed of two 170 MWe independent units, that will supplement the offering of high-output nuclear reactors, especially in response to specific needs such as replacement of fossil-fuelled power plants. NUWARD SMR is a mix of proven and innovative design features that will make it more commercially competitive, while integrating safety features that comply with the highest international standards. Following the principles of redundancy and diversity and rigorous application of Defence in Depth (DID), with an international view on nuclear safety licensing, the Project also incorporates new safety approaches into its design development. The NUWARD SMR Project has been in development for a number of years, it entered conceptual design formally in mid-2019 and entered Basic Design in 2023. The objective of the concept design phase was to confirm the project technological choices and to define the first design configuration of the NUWARD SMR product, to document it, in order to launch pre-licensing with the French Safety Authority (ASN) and to define its estimated cost and its subsequent development and construction schedules. As a delivery milestone the Safety Options file (called the Dossier d'Options de Sûreté (DOS)) has been submitted to ASN in July 2023 for their opinion. An integral part of the NUWARD SMR Project, is not only to deliver a design suitable for France and to satisfy French regulation, but to develop a product suitable and indeed desirable, for the international market, with a first focus in Europe. In order to achieve its objectives and realise its market potential, the NUWARD SMR Project needs to define and realise its safety approach within an international environment and that is the key subject of this paper. The following paper: • Summarises the foundation principles and technological background which underpin the design; • Contextualises the key design features with regard to the international safety regulatory framework with particular emphasis on innovative passive safety aspects; • Illustrates the Project activities in preparation for first licensing in France, and also a wider international view via the ASN led Joint Early Review of the NUWARD SMR design, including Finnish and Czech Republic regulators, recently joined by the Swedish, Polish and Dutch regulators; • Articulates the collaborative approach to design development from involvement with the Project partners (the Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Naval Group, TechnicAtome, Framatome and Tractebel) to the establishment of the International NUWARD Advisory Board (INAB), to gain greater international insight and advice; • Concludes with the focus on next steps into detailed design development, standardisation of the design and its simplification to enhance its commercial competitiveness in a context of further harmonisation of the nuclear safety and licensing requirements and aspirations.

• 한국임상약학회지
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• 제31권1호
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• pp.53-60
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• 2021

Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion: All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission. Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

• 법제연구
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• 제41호
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• pp.229-260
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• 2011

유럽연합에서 회사법 통일의 노력은 리스본조약 이전부터 회사법과 관련한 규칙과 지침을 설정했다는 점에서 중요한 의미를 지닌다. 유럽연합 회사법의 법규범은 자체의 규칙을 통해 유럽주식회사라는 개념을 설정하였으며, 공개유한책임회사인 유럽주식회사와 더불어, 2008년 이후에는 중소기업을 위한 폐쇄유한책임회사에 대한 입법도 추진하고 있다. 최근 유럽주식회사법을 근거로 설립된 회사의 수가 증가되면서 발전된 형태의 회사법에 대한 논의가 활발히 진행되고 있으며, 이는 우리나라 회사법 분야에서도 흥미로운 주제가 된다. 기존의 유럽회사법에 관한 국내연구는 전반적인 유럽회사규칙 및 지침에 대한 내용을 소개하고 있으나, 근래에 이루어지고 있는 회원국 법률간 하향경쟁과 이를 통한 회원국의 입법에서의 변화, 그리고 유럽에서의 회사법연구에 대한 최근 논의에 대해서 다시 다루어 볼 필요가 있다. 따라서 이글에서는 유럽연합조약을 통한 설립의 자유와 이를 통한 각 회원국의 법률 간 경쟁과 유럽주식회사규칙의 제정 배경에 대해서 살펴보고 현재 유럽주식회사규칙의 내용을 평가한다.