• Osong Public Health and Research Perspectives
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• 제8권6호
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• pp.389-396
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• 2017

Objectives: To circumvent the limitations of the current golden standard method, colony-forming unit (CFU) assay, for viability of Bacille Calmette-$Gu{\acute{e}}rin$ (BCG) vaccines, we developed a new method to rapidly and accurately determine the potency of BCG vaccines. Methods: Based on flow cytometry (FACS) and fluorescein diacetate (FDA) as the most appropriate fluorescent staining reagent, 17 lots of BCG vaccines for percutaneous administration and 5 lots of BCG vaccines for intradermal administration were analyzed in this study. The percentage of viable cells measured by flow cytometry along with the total number of organisms in BCG vaccines, as determined on a cell counter, was used to quantify the number of viable cells. Results: Pearson correlation coefficients of FACS and CFU assays for percutaneous and intradermal BCG vaccines were 0.6962 and 0.7428, respectively, indicating a high correlation. The coefficient of variation value of the FACS assay was less than 7%, which was 11 times lower than that of the CFU assay. Conclusion: This study contributes to the evaluation of new potency test method for FACS-based determination of viable cells in BCG vaccines. Accordingly, quality control of BCG vaccines can be significantly improved.

• 한국환경독성학회:학술대회논문집
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• 한국환경독성학회 2002년도 추계국제학술대회
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• pp.168-168
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• 2002

To establish a test protocol for the rodent 20-day thyroid/pubertal assay, flutamide and diethylstilbestrol (DES) were administered to intact male Sprague-Dawley rats from postnatal day 33 for 20 days. Flutamide (1, 5, and 25 mg/kg/day) or DES (10, 20, and 40 ug/kg/day) was given once daily by oral gavage to immature male rats. Prepuce separation was significantly delayed in flutamide group and in DES group. One day after the last dose, the rats were killed and pituitary, thyroid, and reproductive organs were removed and weighed. Flutamide treatment resulted in a significant reduction in the weights of epididymides, ventral prostate, seminal vesicles plus coagulating glands and fluid (SVCGF), levator ani. bulbocarvenus muscles (LABC), Cowper's glands, and glans penis. The weight of adrenal glands decreased at % mg/kg/day, while testes and any other organ weights were unaffected. No microscopic changes were observed in the thyroid glands. Serum levels of testosterone wert significantly increased in the flutamide-treated groups and serum levels of estradiol were also increased. A significant reduction in the weights of testes, epididymides, ventral prostate, SVCGF, LABC, Cowpers glands, and glans penis of DES treated group. Serum testosterone and LH decreased significantly in DES group. Decrease of estradiol was observed, but not significant. These results indicate that flutamide and DES delay puberty in the male rat and its mode of action appears to be via altered secretion of steroids, which subsequently affect the development of the reproductive tract. (Supported by the grant from NITR/Korea FDA for Endocrine Disrupter Research.)

• 한국식품과학회지
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• 제45권3호
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• pp.285-292
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• 2013

Ametoctradin은 triazolopyrimidine계에 속하는 살균제로 역병탄저병을 예방하는 약제이다. 증기압은 $2.1{\times}10^{-10}$ Pa ($20^{\circ}C$)으로 매우 낮아 분석을 위한 기기로 LC를 선택하였으며, HPLC-PDA기기를 사용하여 210 nm에서 400 nm까지 스캔한 결과, 최대흡광파장을 292 nm으로 확인하고 이를 분석파장으로 선택하였다. 추출용매는 물질의 용해도를 고려하여 methanol로 선정하였으며, 액-액 분배 및 정제과정에서는 약제의 n-octanol/water 분배계수($logP_{ow}$, $25^{\circ}C$)가 4.40 (pH 7, $20^{\circ}C$)의 비극성의 물리화학적 특징을 가짐을 고려하여 액-액 분배 단계에서는 dichloromethane, 정제 단계에서는 acetone/hexane (30/70, v/v)을 분석을 위한 용매로 사용하였다. 특히, 컬럼 충진제로 유지, 색소의 비용출성이 우수하고 극성의 물질을 넓은 범위에서 흡착하는 특성을 가지는 florisil을 선택하여 약제에 대한 선택성을 높일 수 있었다. 본 분석법은 회수율 측정(71.9-112.6%)을 통해 코덱스 가이드라인(CAC/GL 40)인 회수율 70-120%, 분석오차 10 미만에 적합함을 보여주어 분석법의 정확성을 확인하였으며, LC-MS를 통한 재확인 과정을 수행함으로써 시험법의 신뢰성과 선택성을 확보할 수 있었다. 또한 재현성을 위해 실험실간 검증을 실시하였으며 그 결과, RSDR(%)는 >0.01 mg/kg, ${\leq}0.1\;mg/kg$범위에서 3.02-14.63%, >0.1 mg/kg범위에서 1.27-7.67%로 코덱스 가이드라인 기준에 적합한 것으로 나타났다. 따라서 본 연구에서 개발한 시험법은 농산물에 잔류하는 ametoctradin을 분석하기 위한 공정 시험법으로 활용할 수 있을 것으로 판단된다.

• The Korean Journal of Medicine
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• 제93권6호
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• pp.501-508
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• 2018

Obesity is a chronic disorder that is a significant risk factor for diabetes, cardiovascular diseases, malignancy, and other chronic diseases. Lifestyle modifications form the basis of most treatments for obesity, but it has become clear that such modifications alone are not enough for many obese patients. When a behavioral approach is insufficient, pharmacological treatment may be recommended. In recent years, the US Food and Drug Administration (FDA) has withdrawn several therapeutic options for obesity due to their side effects, but has approved four novel anti-obesity agents. Until recently, orlistat was the only drug approved for the management of long-term obesity, but the US FDA approved the novel anti-obesity drugs lorcaserin and phentermine/topiramate in 2012, and naltrexone/bupropion and liraglutide in 2014. The present review discusses the different pharmacotherapeutic options for the treatment of obesity.

• 한국임상약학회지
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• 제34권1호
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• pp.39-61
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• 2024

Background: The Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the Ministry of Food and Drug Safety (MFDS) have been implementing the expedited programs that promote the innovative approval of new medications to be used for serious diseases. The authors comprehensively investigated, analyzed, and compared the regulations and guidelines associated with the expedited programs. Methods: The expedited programs for innovative drug development and approval were searched from the homepages of FDA, EMA and MFDS. The detailed information on the regulations and guidelines associated with the programs was comprehensively extracted from various electronic repositories of each regulatory authority. The information on each program was analyzed, categorized, and compared from the points of benefits, applicability with scientific rationale, application procedure, and maintenance. Results: FDA's programs include Fast Track Designation, Breakthrough Therapy Designation, Priority Review Designation, and Accelerated Approval. EMA's regulation implements PRIority MEdicines (PRIME), Accelerated Assessment, Marketing Authorization under Exceptional Circumstances (MAEC), and Conditional Marketing Authorization (CMA). MFDS has a single Expedited Program. These programs are broadly categorized into those that 1) facilitate early and proactive communication with regulatory authorities, 2) shorten the review time after submitting a marketing application, and 3) temporarily approve a marketing authorization under certain conditions. Conclusion: Each expedited program requires a different level and amount of safety and efficacy evidence to be submitted to each regulatory authority. This article will likely provide the comprehensive information on which program provides scientific and regulatory advantages to be taken for innovative medication development.

• 약학회지
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• 제52권5호
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• 대한소아치과학회지
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• 제45권3호
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• pp.393-399
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• 2018

치과치료 중에 통증을 유발할 수 있는 요소를 차단함으로써 환자의 공포와 두려움을 줄여줄 수 있다. 이를 위해 벤조케인을 함유한 도포마취제가 광범위하게 사용되고 있다. 그러나, 2018년 5월 28일 식품의약품안전처는 의약품 안전 서한을 통해 24개월 미만의 소아 및 영아에서 벤조케인 함유 제제의 사용을 금지하고 그 이상의 경우라 하더라도 메트헤모글로빈혈증(Methemoglobinemia, MHb)의 발생가능성이 있으므로 신중한 사용을 권고하였다. 이는 지난 5월 23일 미국 식품의약국(Food and Drug Administration, FDA)의 권고의 후속 조치로 시행된 것이다. 벤조케인을 함유한 제제를 사용하는 경우, 치과의사는 MHb의 발생가능성을 반드시 고려해야 하며 MHb의 조기 진단과 적절한 조치가 시행될 수 있도록 준비하고 있어야한다. MHb의 치료제는 메틸렌블루가 1930년대부터 이용되고 있다. 치과의사는 메틸렌블루의 적절한 사용법과 용량을 숙지하고, MHb의 조기 진단을 위한 방법과 진단 장비에 익숙해야 한다. 무엇보다도 환자의 안전에 대한 적절한 대비와 훈련이 필요할 것이다.

• 응용통계연구
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• 제18권1호
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• pp.159-171
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• 2005

최근 미국을 위시한 선진국에서 제제간의 생물학적 동등성을 판단하는 기준이 생체 이용률의 평균치를 비교하는 시험에서 분산까지 같이 고려하는 기준으로 바뀌고 있다. 처방성과 교차사용성을 의미하는 모집단과 개인 생물학적 동등성이 바로 그것이다. US FDA에서는 2 × 4 교차설계법을 활용해서 제제간의 생동성을 입증하는 것을 추천하고 있다. 현재 US FDA에서 제안하고 있는 모집단 생물학적 동등성 평가 방법은 통계적으로 문제점을 가지고 있어 최근 Lee, Shao & Chow(2002), Chow, Shao & Wang(2003), 그리고 McNally, Iyer & Mathew(2002)에 의해서 수정된 평가 방법들이 제안되고 있다. 본 연구 논문에서는 그동안 제제간의 생물학적 동등성 평가 설계법이였던 2×2 교차설계법을 이용해서 모집단 생물학적 동등성을 평가하는 방법을 논의하고 최근 제안된 방법들을 모의실험을 통해 비교하여 가장 적절한 방법론을 제안한다.

• 한국임상약학회지
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• 제26권2호
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• pp.150-162
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• 2016

Objective: First-in-human dose estimation is an essential approach for successful clinical trials for drug development. In this study, we systematically compared first-in-human dose and human pharmacokinetic parameter estimation approaches. Methods: First-in-human dose estimation approaches divided into similar drug comparison approaches, regulatory guidance based approaches, and pharmacokinetic based approaches. Human clearance, volume of distribution and bioavailability were classified for human pharmacokinetic parameter estimation approaches. Results: Similar drug comparison approaches is simple and appropriate me-too drug. Regulatory guidance based approaches is recommended from US Food and Drug Administration (FDA) and European Medicines Agency (EMA) regarding no-observed-adverse-effect level (NOAEL) or minimum anticipated biological effect level (MABEL). Pharmacokinetic based approaches are 8 approaches for human clearance estimation, 5 approaches for human volume of distribution, and 4 approaches for human bioavailability. Conclusion: This study introduced and compared all methods for first-in-human dose estimation. It would be useful practically to estimate first-in-human dose for drug development.

• 한국식품과학회지
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• 제37권4호
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• pp.671-677
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• 2005

최근 식중독 발생이 대형화됨에 따라 식중독 예방과 식품의 위생적 생산관리를 위하여 식품제조시설에서의 살균소독제 사용 요구가 증가되는 추세이다. 또한 미국 FDA에서는 E. coli와 S. aureus에 대하여 $5\;log_{10}$ CFU/mL의 균수를 감소시키는 화학제제를 살균소독제로 인정하고 있다. 국내에서 유통되는 11종의 살균소독제와 5가지 식품 위해 미생물인 P. aeruginosa, E. coli, S. typhimurium, S. aureus, E. hirae를 대상으로 살균소독제의 유효성을 평가한 결과 현재 시중에서 유통되고 있는 살균소독제 중 자몽추출물과 chlorine를 원료로 사용하는 일부 품목의 경우 법적허용기준인 $5\;log_{10}$ CFU/mL의 살균효과에 미치지 못하는 것으로 판단되었다.