• Korean Journal of Clinical Pharmacy
• /
• v.34 no.1
• /
• pp.39-61
• /
• 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.

• Microbiology and Biotechnology Letters
• /
• v.42 no.1
• /
• pp.1-10
• /
• 2014

Most microorganisms have been used for foods for such a long period of time with no question posed for their safety. However, the progress of food processing technology has activated international food trades, and the consumers and authorities of import countries have come to question the safety of microorganisms used in foods. At present, the most widely known safety standards are Generally Recognized as Safe (GRAS) status from the US Food and Drug Administration (FDA) and Qualified Presumption of Safety (QPS) status by the European Food Safety Authority (EFSA). GRAS status is not for the safety of microorganisms themselves but for the permissibility of strains or cultures in specific food uses. QPS provides a qualified generic approval to a defined taxonomic unit. The increase of commercialized traditional fermented foods in Korea has spurred the starter development for traditional food fermentations. However, starter development in Korea has been carried out based on the technological properties of microorganisms with no research on developing a standardized tool for safety assessment. In the globalization of traditional Korean fermented foods, technological properties as well as safety of future starters should be guaranteed, and establishment of the safety assessment regulation for microorganisms used for foods is necessary.

• Journal of Food Hygiene and Safety
• /
• v.31 no.5
• /
• pp.311-318
• /
• 2016

Azorubine is a synthetic tar color containing azo-bond in the molecular structure. This food colorant has been allowed to be used for beverages, cheese and dried fruits in the European Union and for some food in Australia. Even though it is applicable as a food color in many countries, this compound has not been permitted in Korea so far as a food additive. Thus, this study was performed to establish an analysis method for azorubine in Korea by comparison of three HPLC analysis methods for azorubine and other azo-compounds which are officially used in the European Food Safety Authority (EFSA, EU), the Food Standard Agency (FSA, England) and the National Institute of Food and Drug Safety Evaluation (NIFDS, Korea). The analysis method of the FSA for azorubine showed the best linearity ($r^2=0.999$), limit of detection (LOD, $0.07{\mu}g/mL$), limit of quantification (LOQ, $0.20{\mu}g/mL$), precision (0~0.5%) and accuracy (98.6~100.7%) among tested HPLC methods using a C-18 column and diode array detector (DAD) with ammonium acetate solution and acetonitrile as an eluent solution. Finally selected method of FSA was further verified by inter-day and intra-day experiments with linearity, LOD, LOQ, precision and accuracy. Recovery test showed the recover ratios of 97~103%, 95~101%, and 93~102% in beverages, breads/snacks and other foods, respectively. Inter-laboratory test represented the absolute value of z-score of less than 2 which means satisfactory levels in this test. Selected method of FSA showed reliable analytical results in application test using food samples collected in commercial markets in Europe.

• Journal of Food Hygiene and Safety
• /
• v.37 no.5
• /
• pp.306-309
• /
• 2022

Probiotics are live microorganisms that confer health benefits onto the host when administered at adequate doses. Most widely used probiotics, such as lactobacilli and bifidobacteria, are known to be elements of healthy gut microflora and hence are not considered a threat to the host. However, probiotics may pose a risk in certain populations with compromised immune systems or defects in gut barrier functions. Herein, we evaluated the safety of Bifidobacterium breve BB077, according to the safety evaluation guidelines for probiotics produced by the National Institute of Food and Drug Safety Evaluation (NIFDS). The results show that B. breve BB077 is both non-hemolytic and non-cytolytic. In contrast, B. breve BB077 exhibited higher streptomycin and tetracycline resistance than the suggested NIFDS standard cut-off values. Hence, a genetic analysis of the streptomycin and tetracycline resistance genes was performed to determine the origin of antimicrobial resistance. Streptomycin and tetracycline resistance was shown have arisen from chromosomal mutations and considered intrinsic to the taxonomic group. In conclusion, the B. breve BB077 strain might be safe for human consumption.

• Food Science and Preservation
• /
• v.30 no.3
• /
• pp.538-545
• /
• 2023

This study aimed to assess the in vitro safety of a probiotics mixture (Lactobacillus acidophilus PBS066, Lactiplantibacillus plantarum PBS067, and Limosilactobacillus reuteri PBS072), along with its inhibitory effect on carbohydrate digestion. All three strains met the antibiotic resistance profile of the European Food Safety Authority (EFSA) guidelines. None of the strains exhibited hemolytic activity or cytotoxicity against Caco-2 cells. Strains PBS067 and PBS072 inhibited α-amylase activity, whereas all three strains suppressed α-glucosidase activity, indicating that the mixture might limit carbohydrate digestion in the gastrointestinal tract. These findings support the safety of this probiotics mixture and its potential to modulate carbohydrate metabolism in the gut.

• Journal of Microbiology and Biotechnology
• /
• v.22 no.11
• /
• pp.1510-1517
• /
• 2012

To evaluate the probiotic potential of Bacillus polyfermenticus CJ6 isolated from meju, a Korean traditional soybean fermentation starter, its functionality and safety were investigated. B. polyfermenticus CJ6 was sensitive to all antibiotics listed by the European Food Safety Authority. The strain was also non-hemolytic, carried no emetic toxin or enterotoxin genes, and produced no enterotoxins. The resistance of B. polyfermenticus CJ6 vegetative cells and spores to simulated gastrointestinal conditions was high (60-100% survival rate). B. polyfermenticus CJ6 produced high amounts (0.36 g as a purified lyophilized form) of ${\gamma}$-polyglutamic acid (PGA). We speculate that the improved cell viability and the production of ${\gamma}$-PGA have a significant correlation. Adhesion of the strain to Caco-2 and HT-29 cells was weaker than that of the reference strain (Lb. rhamnosus GG), but it was comparable to or stronger than those of reported Bacillus spp. When B. polyfermenticus CJ6 spores were given orally to mice, the number of cells excreted in the feces was 4-fold higher than the original inocula. This suggests the inoculated spores propagated within the intestinal tract of the mice. This idea was confirmed by field emission scanning electron microscopy, which revealed directly that B. polyfermenticus CJ6 cells germinated and adhered within the gastrointestinal tract of mice. Taken together, these findings suggest that B. polyfermenticus CJ6 has probiotic potential for both human consumption and use in animal feeds.

• Journal of Dairy Science and Biotechnology
• /
• v.32 no.2
• /
• pp.141-145
• /
• 2014

There is a burgeoning number of products on the market that contain probiotics, but do they do you any good? What exactly are probiotics? They have been defined as living organisms that, when ingested in sufficient quantities, provide health benefits beyond basic nutrition. They are often referred to as "friendly bacteria" or "good bacteria." Probiotics have been claimed, amongst other things, to (i) reduce the incidence of colon cancer and other diseases of the colon, such as IBS, (ii) stimulate the immune system, (iii) have anti-hypertensive and anti-cholesterolemic properties, (iv) mitigate against the effect of antibiotics on the intestinal microbiota, and (v) protect against gastrointestinal infections. However, the scientific basis for many of these claims is not well-established. Indeed, the European Food Safety Authority has denied the use of several health claims associated with probiotics, particularly those related to mitigation of diarrhea following consumption of antibiotics. Thus, there is a need for research on the mechanisms of action of probiotics. We have been mainly interested in the use of probiotics to control enteric infections. There are several possible modes of action to explain how probiotics may protect the host from enteric pathogens, including competitive exclusion and immunomodulation. We have shown that probiotics produce bioactive molecules that interfere with bacterial cell-cell communication (also called quorum sensing), and this results in a down-regulation of virulence genes that are responsible for attachment of the pathogen to the gastrointestinal epithelium. These bioactive molecules act on a variety of bacteria, including enterohemorrhagic and enterotoxigenic Escherichia coli, Salmonella, Clostridium difficile and Clostridium perfringens, and there is evidence that they can inhibit the formation of biofilms by Listeria monocytogenes. These bioactive molecules, which are peptidic in nature, can exert their effects not only in vitro but also in vivo, and we have shown that they mitigate against E. coli O157:H7 and Salmonella in mice and Salmonella and E. coli K88 infections in pigs. They can be delivered in foods such as yoghurt and maintain their activity.

• Journal of Animal Science and Technology
• /
• v.66 no.1
• /
• pp.232-236
• /
• 2024

Ligilactobacillus is a genus of Gram-positive lactobacilli commonly found in the intestinal tracts of vertebrates. It has been granted a Qualified Presumption of Safety (QPS) status from the European Food Safety Authority (EFSA). One specific strain, Ligilactobacillus salivarius B4311, was isolated from fecal samples of broiler chickens from a farm associated with Chung-Ang University (Anseong, Korea). This strain was observed to have inhibitory effects against Listeria monocytogenes. In this paper, we present the complete genome sequence of Lig. salivarius B4311. The whole genome of strain B4311 comprises 2,071,255 bp assembled into 3 contigs representing a chromosome, repA-type megaplasmid, and small plasmid. The genome contains 1,963 protein-coding sequences, 22 rRNA genes, and 78 tRNA genes, with a guanine + cytosine (GC) content of 33.1%. The megaplasmid of strain B4311 was found to contain the bacteriocin gene cluster for salivaricin P, a two-peptide bacteriocin belonging to class IIb.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.10
• /
• pp.1420-1429
• /
• 2021

The safety of the probiotic strain Q180, which exerts postprandial lipid-lowering effects, was bioinformatically and phenotypically evaluated. The genome of strain Q180 was completely sequenced, and single circular chromosome of 3,197,263 bp without any plasmid was generated. Phylogenetic and related analyses using16S rRNA gene and whole-genome sequences revealed that strain Q180 is a member of Lactiplantibacillus (Lp., formerly Lactobacillus) plantarum. Antimicrobial resistance (AMR) genes were bioinformatically analyzed using all Lp. plantarum genomes available in GenBank, which showed that AMR genes are present differently depending on Lp. plantarum strains. Bioinformatic analysis demonstrated that some mobile genetic elements such as prophages and insertion sequences were identified in the genome of strain Q180, but because they did not contain harmful genes such as AMR genes and virulence factor (VF)- and toxin-related genes, it was suggested that there is no transferability of harmful genes. The minimum inhibition concentrations of seven tested antibiotics suggested by the European Food Safety Authority guidelines were slightly lower than or equal to the microbiological cut-off values for Lp. plantarum. Strain Q180 did not show hemolytic and gelatinase activities and biogenic amine-producing ability. Taken together, this study demonstrated the safety of strain Q180 in terms of absence of AMR genes and VF- and toxin-related genes as a probiotic strain.

• Journal of Food Hygiene and Safety
• /
• v.38 no.6
• /
• pp.409-419
• /
• 2023

Okadaic acid (OA) group toxins, including OA and its analogs, such as dinophysis toxins (DTXs), have been reported to cause diarrheal shellfish poisoning (DSP). These toxins are primarily produced by dinoflagellates and are accumulated in bivalves. Recently, the presence of Dinophysis sp., a causative alga of DSP, has been reported along the coasts of Korea, posing a potential risk of contamination to domestic seafood and exerting an impact on both the production and consumption of marine products. Accordingly, the European Food Safety Authority (EFSA) and the World Health Organization (WHO) have established standards for the permissible levels of OA group toxins in marine products for safety management. Additionally, in line with international initiatives, the domestic inclusion and regulation of DTX2 among the substances falling under the purview of management outlined by the 2022 diarrheal shellfish toxin standard have been implemented. In this study, we reviewed the physicochemical properties of OA group toxins, their various exposure routes (such as acute toxicity, genotoxicity, reproductive and developmental toxicity), and the relative toxicity factors associated with these toxins. We also performed a comparative assessment of the methods employed for toxin analysis across different countries. Furthermore, we aimed to conduct a broad review of human exposure cases and assess the international guideline for risk management of OA group toxins.