• Analytical Science and Technology
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• v.35 no.3
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• pp.93-115
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• 2022

Potential impurities in pharmaceuticals could be produced during manufacture, distribution, and storage and affect quality and safety of pharmaceuticals. In particular, highly reactive impurities could result in carcinogenic (mutagenic) effects on human body. International Conference on Harmonisation (ICH) has provided M7(R1) guideline for "Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk" and recommended an adoption of this guideline to the authorities. ICH M7(R1) guideline provides classification, accepted intakes, and controls of potential impurities in pharmaceuticals. However, since appropriate and unified analytical methods for impurities in pharmaceuticals have not been provided in this guideline, most potential impurities in pharmaceuticals are still difficult to manage and supervise by pharmaceutical companies and regulatory authorities, respectively. In this review, we briefly described definition of unintended mutagenic impurities, basic information in ICH M7(R1) guideline, and analytical methods to determine potential impurities. This review would be helpful to manage and supervise potential impurities in pharmaceuticals by pharmaceutical companies and regulatory authorities.

• Journal of Intelligence and Information Systems
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• v.27 no.3
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• pp.199-230
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• 2021

Innovative new products and services are being launched through the convergence between heterogeneous industries, and social interest and investment in convergence industries such as AI, big data-based future cars, and robots are continuously increasing. However, in the process of commercialization of convergence new products and services, there are many cases where they do not conform to the existing regulatory and legal system, which causes many difficulties in companies launching their products and services into the market. In response to these industrial changes, the current government is promoting the improvement of existing regulatory mechanisms applied to the relevant industry along with the expansion of investment in new industries. This study, in these convergence industry trends, aimed to analysis the existing regulatory system that is an obstacle to market entry of innovative new products and services in order to preemptively predict regulatory issues that will arise in emerging industries. In addition, it was intended to establish a regulatory impact analysis system to evaluate adequacy and prepare improvement measures. The flow of this study is divided into three parts. In the first part, previous studies on regulatory impact analysis and evaluation systems are investigated. This was used as basic data for the development direction of the regulatory impact framework, indicators and items. In the second regulatory impact analysis framework development part, indicators and items are developed based on the previously investigated data, and these are applied to each stage of the framework. In the last part, a case study was presented to solve the regulatory issues faced by actual companies by applying the developed regulatory impact analysis framework. The case study included the autonomous/electric vehicle industry and the Internet of Things (IoT) industry, because it is one of the emerging industries that the Korean government is most interested in recently, and is judged to be most relevant to the realization of an intelligent information society. Specifically, the regulatory impact analysis framework proposed in this study consists of a total of five steps. The first step is to identify the industrial size of the target products and services, related policies, and regulatory issues. In the second stage, regulatory issues are discovered through review of regulatory improvement items for each stage of commercialization (planning, production, commercialization). In the next step, factors related to regulatory compliance costs are derived and costs incurred for existing regulatory compliance are calculated. In the fourth stage, an alternative is prepared by gathering opinions of the relevant industry and experts in the field, and the necessity, validity, and adequacy of the alternative are reviewed. Finally, in the final stage, the adopted alternatives are formulated so that they can be applied to the legislation, and the alternatives are reviewed by legal experts. The implications of this study are summarized as follows. From a theoretical point of view, it is meaningful in that it clearly presents a series of procedures for regulatory impact analysis as a framework. Although previous studies mainly discussed the importance and necessity of regulatory impact analysis, this study presented a systematic framework in consideration of the various factors required for regulatory impact analysis suggested by prior studies. From a practical point of view, this study has significance in that it was applied to actual regulatory issues based on the regulatory impact analysis framework proposed above. The results of this study show that proposals related to regulatory issues were submitted to government departments and finally the current law was revised, suggesting that the framework proposed in this study can be an effective way to resolve regulatory issues. It is expected that the regulatory impact analysis framework proposed in this study will be a meaningful guideline for technology policy researchers and policy makers in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.2
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• pp.447-450
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• 2004

Overall migration through epoxy layer coated wood was investigated to estimate the coating thickness satisfying the regulatory limit. As an index of overall migration, KMnO$_4$ oxidizable extractives by the food simulant water solution was used. Migration pattern in interest range could described by a simple diffusion model and the temperature dependence of the permeability index could be explained by Arrhenius equation. The thickness of epoxy coating greater than 0.004 mm was analyzed to be required for satisfying the regulatory guideline.

• Journal of the Korean Society of Marine Environment & Safety
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• v.27 no.3
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• pp.421-428
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• 2021

Identifying which international maritime legal instruments are mandatory or recommendatory is complicated task even for maritime regulatory bodies. Although International Maritime Organization (IMO) had tried to ease the complexity by adopting guidelines on uniform wordings for making reference to other instruments in IMO parent conventions, there has still been some confusion identifying the mandatory status of IMO instruments. The aim of this study was to map out a step-based guideline to resolve the complexity of the mandatory status of IMO instruments to the maximum extent possible. This study reviewed the history of IMO rule-making process to find the root cause of the problem, then analyzed the approaches of regulatory enforcement bodies to check the practices. In conclusion, readers are directed to find such information as to legal status of IMO instruments and an improvement is proposed to enhance the transparency of information sharing for maritime industry to make better informed decisions.

• Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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• v.19 no.1
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• pp.141-160
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• 2021

Unit 1 of the Kori Nuclear Power Plant (NPP) and Unit 1 of the Wolsong NPP are being prepared for decommissioning; their decommissioning is expected to generate large amounts of intermediate-level, low-level, and very low level Waste. Mixed waste containing both radioactive and hazardous substances is expected to be produced. Nevertheless, laws and regulations, such as the Korean Nuclear Safety Act and Waste Management Act, do not define clear regulatory guidelines for mixed waste. However, the United States has strictly enforced regulations on mixed waste, focusing on the human health and environmental effects of its hazardous components. The U.S. Nuclear Regulatory Commission and the U.S. Department of Energy regulate the radioactive components of mixed waste under the Atomic Energy Act. The U.S. Environmental Protection Agency regulates the hazardous waste component of mixed waste under the Resource Conservation and Recovery Act. In this study, the laws, regulations, and authorities pertaining to mixed waste in the United States are reviewed. Through comparison and analysis with waste management laws and regulations in Korea, a treatment direction for mixed waste is suggested. Such a treatment for mixed waste will increase the efficiency of managing mixed waste when decommissioning NPPs in the near future.

• Korean Journal of Clinical Pharmacy
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• v.28 no.2
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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.

• Journal of Integrative Natural Science
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• v.4 no.4
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• pp.315-322
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• 2011

This study was performed to investigate the current regulatory guidances of safety and efficacy evaluation for the approval of stereoisomeric drugs in Korea and US. According to the regulatory guidelines in major countries (EU, Canada, US), the important categories for the development of stereoisomeric drugs are classified as 1) development of a single enantiomer as a new active substances 2) development of a racemate as a new active substance 3) development of a new single enantiomer from an approved racemate. For this study, domestic regulatory documents for current guidelines of stereoisomeric drugs were investigated. Also four typical stereoisomeric drugs for three categories were chosen to investigate the new drug submission documents of KFDA and FDA for the safety and efficacy evaluation of stereoisomeric drugs. It is expected that these comparative results between KFDA and FDA will be useful for the safety and efficacy for the regulatory approval of stereoisomeric drugs in Korea.

• International Journal of Stem Cells
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• v.17 no.2
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• pp.147-157
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• 2024

The objective of standard guideline for utilization of human lung organoids is to provide the basic guidelines required for the manufacture, culture, and quality control of the lung organoids for use in non-clinical efficacy and inhalation toxicity assessments of the respiratory system. As a first step towards the utilization of human lung organoids, the current guideline provides basic, minimal standards that can promote development of alternative testing methods, and can be referenced not only for research, clinical, or commercial uses, but also by experts and researchers at regulatory institutions when assessing safety and efficacy.

• International Journal of Stem Cells
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• v.17 no.2
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• pp.130-140
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• 2024

Cardiac organoids have emerged as invaluable tools for assessing the impact of diverse substances on heart function. This report introduces guidelines for general requirements for manufacturing cardiac organoids and conducting cardiac organoid-based assays, encompassing protocols, analytical methodologies, and ethical considerations. In the quest to employ recently developed three-dimensional cardiac organoid models as substitutes for animal testing, it becomes imperative to establish robust criteria for evaluating organoid quality and conducting toxicity assessments. This guideline addresses this need, catering to regulatory requirements, and describes common standards for organoid quality and toxicity assessment methodologies, commensurate with current technological capabilities. While acknowledging the dynamic nature of technological progress and the potential for future comparative studies, this guideline serves as a foundational framework. It offers a comprehensive approach to standardized cardiac organoid testing, ensuring scientific rigor, reproducibility, and ethical integrity in investigations of cardiotoxicity, particularly through the utilization of human pluripotent stem cell-derived cardiac organoids.

• Toxicological Research
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• v.34 no.2
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• pp.111-125
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• 2018

Solvents can be used in the manufacture of medicinal products provided their residual levels in the final product comply with the acceptable limits based on safety data. At worldwide level, these limits are set by the "Guideline Q3C (R6) on impurities: guideline for residual solvents" issued by the ICH. Diisopropyl ether (DIPE) is a widely used solvent but the possibility of using it in the pharmaceutical manufacture is uncertain because the ICH Q3C guideline includes it in the group of solvents for which "no adequate toxicological data on which to base a Permitted Daily Exposure (PDE) was found". We performed a risk assessment of DIPE based on available toxicological data, after carefully assessing their reliability using the Klimisch score approach. We found sufficiently reliable studies investigating subchronic, developmental, neurological toxicity and carcinogenicity in rats and genotoxicity in vitro. Recent studies also investigated a wide array of toxic effects of gasoline/DIPE mixtures as compared to gasoline alone, thus allowing identifying the effects of DIPE itself. These data allowed a comprehensive toxicological evaluation of DIPE. The main target organs of DIPE toxicity were liver and kidney. DIPE was not teratogen and had no genotoxic effects, either in vitro or in vivo. However, it appeared to increase the number of malignant tumors in rats. Therefore, DIPE could be considered as a non-genotoxic animal carcinogen and a PDE of 0.98 mg/day was calculated based on the lowest No Observed Effect Level (NOEL) value of $356mg/m^3$ (corresponding to 49 mg/kg/day) for maternal toxicity in developmental rat toxicity study. In a worst-case scenario, using an exceedingly high daily dose of 10 g/day, allowed DIPE concentration in pharmaceutical substances would be 98 ppm, which is in the range of concentration limits for ICH Q3C guideline class 2 solvents. This result might be considered for regulatory decisions.