Ministry Of Food And Drug Safety Research Articles

Clinical Trial Protocol for Porcine Islet Xenotransplantation in South Korea.

Islet transplantation holds promise for treating selected type 1 diabetes mellitus patients, yet the scarcity of human donor organs impedes widespread adoption. Porcine islets, deemed a viable alternative, recently demonstrated successful longterm survival without zoonotic risks in a clinically relevant pig-to-non-human primate islet transplantation model. This success prompted the development of a clinical trial protocol for porcine islet xenotransplantation in humans. A single-center, open-label clinical trial initiated by the sponsor will assess the safety and efficacy of porcine islet transplantation for diabetes patients at Gachon Hospital. The protocol received approval from the Gachon Hospital Institutional Review Board (IRB) and the Korean Ministry of Food and Drug Safety (MFDS) under the Investigational New Drug (IND) process. Two diabetic patients, experiencing inadequate glycemic control despite intensive insulin treatment and frequent hypoglycemic unawareness, will be enrolled. Participants and their family members will engage in deliberation before xenotransplantation during the screening period. Each patient will receive islets isolated from designated pathogen-free pigs. Immunosuppressants and systemic infection prophylaxis will follow the program schedule. The primary endpoint is to confirm the safety of porcine islets in patients, and the secondary endpoint is to assess whether porcine islets can reduce insulin dose and the frequency of hypoglycemic unawareness. A clinical trial protocol adhering to global consensus guidelines for porcine islet xenotransplantation is presented, facilitating streamlined implementation of comparable human trials worldwide.

Regulatory Framework for Drug-Device Combination Products in the United States, Europe, and Korea.

Combination products (CPs) combine two or more product types such as drugs, devices, and/or biological products for increased safety and clinical effectiveness. The emergence of innovative CPs poses new challenges for regulatory agencies in assigning jurisdiction for premarket review and oversight. In US, the 1990 Safe Medical Devices Act defines and provides classification criteria for CPs, and the US government has developed a regulatory process through multiple acts, including the 21st Century Cures Act of 2016. Meanwhile, regulators in the European Union (EU) and the Republic of Korea have recently recognized the importance of premarket pathways for CPs. The European Medicines Agency (EMA) has issued guidelines and explanations on compliance issues related to drug-device CPs under MDR. EMA doesn't have the definitions of CPs, but uses the term drug-device combination products (drug-device CPs). CPs are categorized as drugs or medical devices, which follow their relevant regulatory framework. The Ministry of Food and Drug Safety (MFDS) in Korea has legal definitions of CPs under the Notice of the MFDS. CPs are designated as drugs or medical devices according to their primary mode of actions (PMOA) and follow regulatory processes through the framework of drugs or medical devices. This study aims to comprehensively summarize the regulatory oversight of CPs by analyzing the regulatory policies and legal frameworks in the US, the EU, and Korea. The regulatory challenges encountered when developing CPs are also discussed. With specific emphasis on the combination of drugs and devices, this study provides in-depth insights into the regulatory landscape, shedding light on the unique challenges associated with the development of CPs for this particular intersection of drugs and devices.

Analytical Method Development and Dermal Absorption of 4-Amino-3-Nitrophenol (4A3NP), a Hair Dye Ingredient under the Oxidative or Non-Oxidative Condition.

The chemical 4-amino-3-nitrophenol (4A3NP) is classified as an amino nitrophenol and is primarily utilized as an ingredient in hair dye colorants. In Korea and Europe, it is exclusively used in non-oxidative or oxidative hair dye formulations, with maximum allowable concentrations of 1% and 1.5%, respectively. Despite this widespread use, risk assessment of 4A3NP has not been completed due to the lack of proper dermal absorption data. Therefore, in this study, both the analytical method validation and in vitro dermal absorption study of 4A3NP were conducted following the guidelines provided by the Korea Ministry of Food and Drug Safety (MFDS). Before proceeding with the dermal absorption study, analytical methods were developed for the quantitation of 4A3NP through multiple reaction monitoring (MRM) via liquid chromatography-mass spectrometry (LC-MS) in various matrices, including swab wash (WASH), stratum corneum (SC), skin (SKIN, comprising the dermis and epidermis), and receptor fluid (RF). These developed methods demonstrated excellent linearity (R2 = 0.9962-0.9993), accuracy (93.5-111.73%), and precision (1.7-14.46%) in accordance with the validation guidelines.The dermal absorption of 4A3NP was determined using Franz diffusion cells with mini-pig skin as the barrier. Under both non-oxidative and oxidative (6% hydrogen peroxide (H2O2): water, 1:1) hair dye conditions, 1% and 1.5% concentrations of 4A3NP were applied to the skin at a rate of 10 μL/cm2, respectively. The total dermal absorption rates of 4A3NP under non-oxidative (1%) and oxidative (1.5%) conditions were determined to be 5.62 ± 2.19% (5.62 ± 2.19 μg/cm2) and 2.83 ± 1.48% (4.24 ± 2.21 μg/cm2), respectively.

The Accomplishments of KoCVAM in the Development and Implementation of Alternative Methods in Korea.

The Korean Center for the Validation of Alternative Methods (KoCVAM), which promotes the Three Rs principles and the use of alternative methods in Korea, has been operating within the Toxicological Screening and Testing Division of the Ministry of Food and Drug Safety (MFDS) since 2009. KoCVAM has exchanged opinions and information on the development and validation of non-animal alternative test methods as part of the International Cooperation on Alternative Test Methods (ICATM), and provided input into draft OECD Test Guidelines (TGs). Several Korean laws (e.g. the Cosmetics Act) encourage the use of alternative test methods for chemical testing and assessment. To promote and support the use of alternative test methods in the country, KoCVAM has published information and provided training on the national guidelines, which are based on the OECD TGs. In addition, KoCVAM has held annual training workshops on alternative test methods, to help Korean research institutions (including GLP test facilities) to implement them. In addition, by helping to develop and validate alternative test methods that were adopted in OECD TG 442B, TG 492 and TG 439, KoCVAM has contributed to the enhanced competitiveness of Korean industry on the worldwide stage.

Validation study of isoflavone derivatives and simultaneous analysis of Puerariae Flos

Using LC/MS, isoflavones (glycitin, genistin, tectoridin, glycitein, genistein, and tectorigenin) known as Puerariae Flos marker compounds were identified. The simultaneous analysis and validation of six marker compounds were performed using the HPLC-DAD method. To validate the analysis method of six marker compounds 1–6, the linearity was showed in the calibration curve as coefficient of correlation (R2) range of 0.9997–1.000. The limit of detection (LOD) and limit of quantitation (LOQ) of six marker compounds were measured in the ranges of 0.2720–0.7884 µg/mL and 0.8243–2.3890 µg/mL, respectively. Intermediate precision, repeatability, and accuracy evaluations according to the Ministry of Food and Drug Safety (MFDS) guidelines showed that the relative standard deviation (RSD) less than 1% and the stability less than 2%, respectively. Also, the simultaneous validation method is attributed to analysis of the different isoflavones Flos ne compounds in Puerariae extract. It could be potentially used as sources of pharmaceutical and natural antioxidant ingredients.

Report on the seventh meeting of national control laboratories for vaccines and biologicals of the WHO Western Pacific and South-East Asia member states

The Biregional Network of National Control Laboratories (NCLs) of the WHO Western Pacific and South-East Asia Regions has been meeting annually since 2018 to enhance NCLs' voluntary participation capacity. Its seventh meeting was hosted by the Korea National Institute of Food and Drug Safety Evaluation (NIFDS) of the Ministry of Food and Drug Safety (MFDS), in conjunction with the Global Bio Conference, in Seoul on September 6, 2022. Over 60 participants from seven countries, (India, Indonesia, Japan, Korea, Malaysia, the Philippines, and Vietnam) attended the meeting on-site and online. The theme of this meeting was ‘Quality Control Issues and International Trends for Biologicals including Vaccines and Plasma-Derived Medicinal Products.’ Three special speeches were presented on sharing the quality control system for biologicals, including NCLs' considerations in preparing the WHO Listed Authorities and sharing MFDS experiences. Furthermore, the participating NCLs shared country-specific issues related to national lot releases during the COVID-19 pandemic and acknowledged the meeting’s crucial role in response preparedness for pandemic emergencies and enhancing regulatory capacity through coalitions and information exchange among NCLs. The NIFDS will cooperate closely with other Asian NCLs to enhance biological product quality control, aiming to establish regional standards and standardize test methods through collaboration.

Current clinical trial disclosure landscape in Asia

The transparency and disclosure landscape in Asia has been rapidly evolving during the past decade. With respect to clinical trial registries, China launched its national registry, ChinaDrugTrials.org.cn, in 2013; South Korea introduced the new clinical trial disclosure platform through its Ministry of Food and Drug Safety (MFDS) in 2019; whilst Japan unified its three existing primary registries into a single clinical trial registry – Japan Registry of Clinical Trials (jRCT) – in 2020. We provide an overview of the national clinical trial registries and the trial results disclosure practices for 4 Asian countries – China, Japan, South Korea, and Taiwan.

Gut microbial change after administration of Lacticaseibacillus paracasei AO356 is associated with anti-obesity in a mouse model.

The status of an impaired gut microbial community, known as dysbiosis, is associated with metabolic diseases such as obesity and insulin resistance. The use of probiotics has been considered an effective approach for the treatment and prevention of obesity and related gut microbial dysbiosis. The anti-obesity effect of Lacticaseibacillus paracasei AO356 was recently reported. However, the effect of L. paracasei AO356 on the gut microbiota has not yet been identified. This study aimed to elucidate the effect of L. paracasei AO356 on gut microbiota and ensure its safety for use as a probiotic. Oral administration of L. paracasei AO356 (107 colony-forming units [CFU]/mg per day, 5 days a week, for 10 weeks) to mice fed a high-fat diet significantly suppressed weight gain and fat mass. We investigated the composition of gut microbiota and explored its association with obesity-related markers. Oral administration of L. paracasei AO356 significantly changed the gut microbiota and modified the relative abundance of Lactobacillus, Bacteroides, and Oscillospira. Bacteroides and Oscillospira were significantly related to the lipid metabolism pathway and obesity-related markers. We also confirmed the safety of L. paracasei AO356 using antibiotics resistance, hemolysis activity, bile salt hydrolase activity, lactate production, and toxicity tests following the safety assessment guidelines of the Ministry of Food and Drug Safety (MFDS). This study demonstrated that L. paracasei AO356 is not only associated with an anti-obesity effect but also with changes in the gut microbiota and metabolic pathways related to obesity. Furthermore, the overall safety assessment seen in this study could increase the potential use of new probiotic materials with anti-obesity effects.

Comparison of pharmacogenomic information for drug approvals provided by the national regulatory agencies in Korea, Europe, Japan, and the United States

Pharmacogenomics, which is defined as the study of changes in the properties of DNA and RNA associated with drug response, enables the prediction of the efficacy and adverse effects of drugs based on patients’ specific genetic mutations. For the safe and effective use of drugs, it is important that pharmacogenomic information is easily accessible to clinical experts and patients. Therefore, we examined the pharmacogenomic information provided on drug labels in Korea, Europe, Japan, and the United States (US). The selection of drugs that include pharmacogenomic information was based on the drug list that includes genetic information from the Korea Ministry of Food and Drug Safety (MFDS) and US Food and Drug Administration (FDA) websites. Drug labels were retrieved from the sites of MFDS, FDA, European Medicines Agency, and Japanese Pharmaceuticals and Medical Devices Agency. Drugs were classified as per the Anatomical Therapeutic Chemical code, and the biomarkers, labeling sections, and necessity of genetic tests were determined. In total, 348 drugs were selected from 380 drugs with available pharmacogenomic information in Korea and the US after applying the inclusion and exclusion criteria. Of these drugs, 137, 324, 169, and 126 were with pharmacogenomics information in Korea, the US, Europe, and Japan, respectively. The most commonly represented drug class was antineoplastic and immunomodulating agents. Regarding the classification as per the mentioned biomarkers, the cytochrome P450 enzyme was the most frequently mentioned information, and the targeted anticancer drugs most commonly required genetic biomarker testing. The reasons for differences in drug labeling information based on country include differences in mutant alleles according to ethnicity, frequencies at which drug lists are updated, and pharmacogenomics-related guidelines. Clinical experts must continuously strive to identify and report mutations that can explain drug efficacy or side effects for safe drug use.

Method validation for quantitative analyzing aflatoxin productivity in Aspergillus sp. isolated from soybean paste

Non-aflatoxigenic Aspergillus oryzae and aflatoxigenic A. flavus cannot be clearly identified by partial sequencing of the internal transcribed spacer (ITS) and 18S ribosomal ribonucleic acid (18S rRNA) regions. This study aimed to compare the accuracy among three aflatoxin detection methods using ultra-performance liquid chromatography (UPLC), high-performance liquid chromatography (HPLC), and an enzyme-linked immunosorbent assay (ELISA) kit and to select the non-aflatoxigenic Aspergillus sp. isolated from soybean paste. All analytical methods were suitable according to the international standards of Codex Alimentarius FAO-WHO (CODEX) or the Ministry of Food and Drug Safety (MFDS). UPLC exhibited the best of limit of detection (LOD) and limit of quantification (LOQ). Based on UPLC, HPLC, and the ELISA kit assay, the P5 and P7 strains isolated from soybean paste had 1,663.49, 1,468.12, and ⟩20 μg/kg and 1,470.08, 1,056.73, and ⟩20 μg/kg, respectively, detected and re-identified as A. flavus. In contrast, the P3 and P4 strains (A. oryzae), which were detected below the MFDS standards in all assays, were confirmed as non-aflatoxigenic fungi. Among the methods evaluated for quantitative analysis of aflatoxin, UPLC and HPLC are superior in terms of accuracy, and the ELISA kit rapidly detects low concentrations of aflatoxin. Furthermore, this study demonstrates that any Aspergillus sp. isolated for use as a fermentation starter should be analyzed for potential aflatoxin production using UPLC and HPLC for accurate quantitative analysis or ELISA for the rapid detection of low-level concentrations of aflatoxin.

Post-Marketing Safety Surveillance of a Childhood Pentavalent Diphtheria-Tetanus-Acellular Pertussis-Polio and Haemophilus influenzae TypeB (DTaP-IPV//Hib) Vaccine in South Korea.

PENTAXIM™ (Sanofi), DTaP-IPV//Hib, a pentavalent combination vaccine for protection against diphtheria, tetanus, pertussis, poliomyelitis, and invasive infections caused by Haemophilus influenzae typeb, has been licensed in South Korea by the Ministry of Food and Drug Safety (MFDS) on May9, 2016, and is currently used in routine vaccination. The aim of this phaseIV study, conducted as a post-licensure commitment in South Korea, was to evaluate the safety of the DTaP-IPV//Hib vaccine when administered in infants at 2, 4, and 6months of age in the real-world clinical practice. This multicenter, observational, post-marketing surveillance (PMS) study was conducted in real-world practice in South Korea. Infants aged 2months or older were enrolled across seven centers from July31, 2018 to February11, 2020. The study outcomes included occurrence, time to onset, duration, intensity, and causality assessment (for unsolicited adverse events [AEs] only) for several pre-listed solicited injection-site and systemic reactions, unsolicited AEs, and serious adverse events (SAEs). Data from 619 participants were included in the safety analysis. Overall, 618 AEs were reported by 273 (44.1%) participants consisting of 121 solicited injection-site reactions (15.4%), 344 solicited systemic reactions (24.6%), and 153 unsolicited AEs (15.7%) of which, 124 were unexpected AEs (12.9%) (regardless of intensity). None of the unsolicited AEs were reported to have a causal relationship with the study vaccine. One SAE of pyrexia (solicited reaction) was reported. Most AEs were of mild intensity, and all participants recovered. This PMS study of the DTaP-IPV//Hib vaccine confirmed its safety profile in a real-life setting in South Korea and justified that the vaccine is well tolerated when used in infants aged 2months or older for the primary series.

Analytical method development and dermal absorption of 2-amino-5-nitrophenol (2A5NP), a hair dye ingredient under oxidative condition.

Although 2-amino-5-nitrophenol (2A5NP) is one of the ingredients of hair dye, there has been no information on the dermal absorption rate of 2A5NP. 2A5NP is managed at less than 1.5% in Korea and Japan. In this study, analytical methods were developed and validated using high-performance liquid chromatography (HPLC) in various matrices of wash, swab, stratum corneum (SC), skin (dermis + epidermis), and receptor fluid (RF). Validation results were acceptable based on Korea Ministry of Food and Drug Safety (MFDS) guideline. The HPLC analysis showed a good linearity (r2 = 0.9992-0.9999), a high accuracy (93.1-110.2%), and a good precision (1.1-8.1%) in accordance with the validation guideline. Franz diffusion cell was used to determine dermal absorption of 2A5NP using mini pig skin. 2A5NP (1.5%) was applied to skin at 10μl/cm2. For certain cosmetic ingredients such as hair dye with short exposure time, an interimwash step (after 30min) was added during the study. After application for 30min and 24h, skin was wiped off with swab and SC was collected using tape stripping. RF was sampled at 0, 1, 2, 4, 8, 12, and 24h. Total dermal absorption rate of 2A5NP (1.5%) was determined to be 13.6 ± 2.9%.

Prevention and Treatment Potential of COVID-19 Infectious Disease Using Edible Perilla Leaf Extracts

Various vaccines for the infectious Coronavirus Disease of 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have already been developed and used, but breakthrough infections continue to occur despite the administration of additional booster injections. Various therapeutic agents are being developed during the pandemic, but their use is still limited. Finding a new drug to treat or prevent COVID-19 takes time and money. As such, repositioning the application of existing drugs or foods with fewer rejections or side effects, even at high doses, could be a solution to the limitations. The usefulness of perilla leaf extract or perilla leaves functional food was confirmed in this study. We examined the possibility of preventing and treating COVID-19 infection with perilla leaves, a leafy vegetable widely consumed as food in Korea. In addition, there is a possibility of using the 70% ethanol extract of perilla leaves, which has the effect of reducing body fat according to the Korean Ministry of Food and Drug Safety (MFDS), as a therapeutic agent during the COVID-19 epidemic. However, proof of efficacy should be confirmed through clinical trials.

공중보건 위기대응 의료제품의 개발 촉진 및 긴급 공급을 위한 특별법 고찰 및 FDA와 EMA의 유사 법안 비교 분석

Since the outbreak of the new strain of coronavirus (SARS-CoV-2, COVID-19) was first reported, regulatory authorities worldwide have issued various regulatory guidelines and recommendations. Global authorities are committed to supporting developers of potential vaccines and treatments for COVID-19. This study reviewed the guidelines and regulatory procedures instituted by authorities in the United States and Europe to understand the current perspectives of regulatory agencies worldwide and derive implications for public health emergency responses. The Act on Encouragement of Development and Emergency Circulation of Medical Countermeasures for public health emergencies enacted in 2021 established the Ministry of Food and Drug Safety (MFDS) to oversee policies for public health emergencies. In the US, the Public Law 113-5, the PHS Act, the PREP Act and the FD&C Act grant authorities emergency use power with respect to medical countermeasures needed during public health emergencies. The FDA can also facilitate the use of those medical countermeasures. The EMA has accelerated regulatory procedures in place for expediting the development and approval of medicinal products for COVID-19. The EMA’s rapid procedure includes rolling review, accelerated assessment and conditional marketing authorisation. Based on the review of foreign policies and practices regarding public health emergencies, this study showed that the Act on Encouragement of Development and Emergency Circulation of Medical Countermeasures for public health emergency responses has made important advances in public health emergency preparedness and response.

Efficacy and safety of Lenzumestrocel (Neuronata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial

BackgroundA single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in patients with ALS but did not demonstrate long-term efficacy. This phase III clinical trial (ALSUMMIT) protocol was developed to evaluate the long-term efficacy and safety of the combined protocol of single-cycle intrathecal therapy and three additional booster injections of BM-MSC (Lenzumestrocel) treatment in patients with ALS.MethodsALSUMMIT is a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial for ALS. The 115 subjects will be randomized (1:2:2) into three groups: (1) study Group 1 (single-cycle, two repeated injections with 26-day interval), (2) study Group 2 (single-cycle + three additional booster injections at 4, 7, and 10 months), and (3) the control group. Participants who have an intermediate rate of disease progression will be included in this trial to reduce clinical heterogeneity. The primary endpoint will be evaluated by combined assessment of function and survival (CAFS), also known as joint rank scores (JRS), at 6 months (study Group 1 vs. control) and 12 months (study Group 2 vs. control) after the first Lenzumestrocel or placebo administration. Safety assessment will be performed throughout the study period. Additionally, after the 56-week main study, a long-term follow-up observational study will be conducted to evaluate the long-term efficacy and safety up to 36 months.DiscussionLenzumestrocel is the orphan cell therapy product for ALS conditionally approved by the South Korea Ministry of Food and Drug Safety (MFDS). This ALSUMMIT protocol was developed for the adoption of enrichment enrolment, add-on design, and consideration of ethical issues for the placebo group.Trial registrationClinicalTrials.govNCT04745299. Registered on Feb 9, 2021.Clinical Research Information Service (CRIS) KCT0005954. Registered on Mar 4, 2021.

Dissipation characteristics of spirotetramat and its metabolites in two phenotypically different Korean vegetables under greenhouse conditions

This study involved analysis and method validation of spirotetramat applied to two phenotypically different Korean vegetables (e.g. Korean cabbage and shallots) to determine the safe pre-harvest residue limit (PHRL) and comparative dissipation patterns. Two steps of the investigation involved greenhouse monitoring during crop cultivation followed by LC-MS/MS analysis. Commercial spirotetramat was sprayed twice with seven-day intervals according to the spray schedule (0, 3, 7, 10, 14, and 21 days before harvest) at the dose recommended by the Ministry of Food and Drug Safety (MFDS), Korea. During the validation of the analytical method, good linearity, specificity, and acceptable recoveries (82%–114% for Korean cabbage and 82%–111% for shallot) were established for spirotetramat and its four metabolites. The calculated biological half-life derived from the first-order reaction (t1/2) of spirotetramat was 4.8 days for Korean cabbage and 4.0 days for shallot, respectively. The safe PHRL for Korean cabbage was suggested at 7 days, due to permissible spirotetramat concentration in terms of an acceptable MRL. The findings of the study will be used as the analytical reference point for developing spirotetramat safety guidelines for use in the vegetables investigated.

Drug Lag and Associated Factors for Approved Drugs in Korea Compared with the United States.

(1) Background: Drug lag, the delay between the first global regulatory approval and approval by the national health authorities in other countries, impacts the accessibility of drugs. Although the Korean pharmaceutical market has grown significantly, most of its innovative drugs for public health depend on imports from foreign pharmaceutical markets. (2) Methods: We extracted data from the official websites of the Korean Ministry of Food and Drug Safety (MFDS) and the US Food and Drug Administration. Information on new molecule entity drugs, approved as imported drugs by MFDS from 2000 to 2019, was extracted. Multivariate Cox proportional hazard models on drug approval were estimated. (3) Results: In total, 424 drugs were analyzed. Orphan drugs designated by MFDS were less likely to receive approval (HR = 0.731, 95% CI: 0.572–0.934). The drugs with Korean MAHs were less likely to obtain drug approval than those with MAHs of subsidiaries of multinational pharmaceutical companies (HR = 0.524, 95% CI: 0.371–0.738). In the analyses for non-orphan drugs (n = 37), oncology drugs that need local clinical study (HR = 0.247, 95% CI: 0.093–0.657) and drugs that need more patients in a local clinical study (HR = 0.993, 95% CI: 0.988–0.999) were less likely to receive approval, with longer drug lag. The higher number of clinical studies in Korea was associated with a shorter drug lag (HR = 2.133, 95% CI: 1.196–3.805). (4) Conclusions: Our findings imply that Korean pharmaceutical companies should augment their research capabilities for new drug development. Furthermore, consideration of orphan drugs used in rare diseases is needed for drug approval to ensure the availability of these drugs in the market without approval delays.

The presence of unauthorized ingredients in dietary supplements: An analysis of the risk warning data in Korea

The Ministry of Food and Drug Safety (MFDS) has identified that numerous dietary supplements contain unapproved (hidden, undeclared, and unauthorized) ingredients that could be unsafe. The aim of this study is to summarize the presence of unapproved ingredients in dietary supplements based on the warning dataset released by the MFDS from 2010 to 2019. The warning data were extracted from the alert system on the MFDS’s website. The highest number (ratio) of products found in the dataset were marketed for sexual enhancement [770 (43.3 %)], weight-loss [690 (38.8 %)], muscular strengthening [243 (13.7 %)], or relaxing [76 (4.3 %)]. A total of 1779 products contained one or more unapproved ingredients. The most common unauthorized compounds were icariin, sildenafil, and tadalafil for sexual enhancement, yohimbine, sibutramine, and sennoside for weight loss, and yohimbine and icariin for muscular strengthening, and melatonin and 5-hydroxytryptophan for relaxing products, respectively. Unapproved ingredients continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after warnings by regulatory authorities. The unauthorized compounds in these dietary supplements have potential adverse health effects on consumers owing to accidental misuse, overuse, interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement. Our study reviewed potential health issues concerning the main unapproved ingredients to contribute to the understanding of adulteration in dietary supplements. The result of this study can be used to elucidate adulteration trends of unapproved ingredients in dietary supplements.

Comparison of Medical Device Regulations in India, Japan and South Korea

Increased health awareness, a growing middle class, and government health efforts are projected to propel India's medical equipment market forward in the next years. With the publication of the Medical Device Rules in 2017, Indian authorities revised the medical device regulatory process. The devices included in the link are currently regulated medical devices and in vitro diagnostic devices, as well as their classifications. CLA (Central Licensing Authority) is in charge of all import device licencing, as well as manufacturing, loan, and wholesale licences for Class C and Class D medical devices.
 Because of its complicated registration process and linguistic obstacles, Japan is regarded one of the most difficult markets for overseas medical device producers. The Pharmaceutical and Medical Device Agency, which works in tandem with the MHLW (Ministry of Health and Labour Welfare), is in charge of reviewing drug and medical device applications in Japan. The Pharmaceuticals and Medical Devices Act is a federal law that regulates the sale of pharmaceuticals and medical devices. The Pharmaceuticals and Medical Devices Act, also known as the Act on Securing Quality, Efficacy, and Safety of Pharmaceuticals, Medical Devices, Regenerative and Cellular Therapy Products, Gene Therapy Products, and Cosmetics, lays out the current PMDA (Pharmaceuticals and Medical devices Agency) laws in Japan.
 South Korea is one of the largest health-care markets in the Asia-Pacific region. Medical Devices in South Korea are regulated by the Ministry of Food and Drug Safety (MFDS), formerly known as the Korea Food and Drug Administration (KFDA). Medical Devices in South Korea are regulated by the Ministry of Food and Drug Safety, formerly known as the Korea Food and Drug Administration. The Medical Device Act of 2015 governs current medical device laws in Korea. To access the South Korean Medical-Device-Market, you must first obtain marketing approval from the local Medical Device Authority, the Medical Device Information & Technology Centre, which is part of the Ministry of Food and Drug Safety. With the MFDS notification No. 2020-29, the South Korean Ministry of Food and Drug Safety launched UDI (Unique Device Identification System) operations in 2018. Article 20 of the Medical Device Act and Article 54-2 of the Medical Device Act Enforcement Regulations make UDI compliance mandatory.

Toxicological Evaluation of a Probiotic-Based Delivery System for P8 Protein as an Anti-Colorectal Cancer Drug.

PurposeThis study aimed to toxicological evaluate a probiotics-based delivery system for p8 protein as an anti-colorectal cancer drug.IntroductionLactic acid bacteria (LAB) have been widely ingested for many years and are regarded as very safe. Recently, a Pediococcus pentosaceus SL4 (PP) strain that secretes the probiotic-derived anti-cancer protein P8 (PP-P8) has been developed as an anti-colorectal cancer (CRC) biologic by Cell Biotech. We initially identified a Lactobacillus rhamnosus (LR)-derived anti-cancer protein, P8, that suppresses CRC growth. We also showed that P8 penetrates specifically into CRC cells (DLD-1 cells) through endocytosis. We then confirmed the efficacy of PP-P8, showing that oral administration of this agent significantly decreased tumor mass (~42%) relative to controls in a mouse CRC xenograft model. In terms of molecular mechanism, PP-P8 induces cell-cycle arrest in G2 phase through down-regulation of Cyclin B1 and Cdk1. In this study, we performed in vivo toxicology profiling to obtain evidence that PP-P8 is safe, with the goal of receiving approval for an investigational new drug application (IND).MethodsBased on gene therapy guidelines of the Ministry of Food and Drug Safety (MFDS) of Korea, the potential undesirable effects of PP-P8 had to be investigated in intact small rodent or marmoset models prior to first-in-human (FIH) administration. The estimated doses of PP-P8 for FIH are 1.0×1010 – 1.0×1011 CFU/person (60 kg). Therefore, to perform toxicological investigations in non-clinical animal models, we orally administered PP-P8 at doses of 3.375 × 1011, 6.75 × 1011, and 13.5×1011 CFU/kg/day; thus the maximum dose was 800–8000-fold higher than the estimated dose for FIH.ResultsIn our animal models, we observed no adverse effects of PP-P8 on clinicopathologic findings, relative organ weight, or tissue pathology. In addition, we observed no inflammation or ulceration during pathological necropsy.ConclusionThese non-clinical toxicology studies could be used to furnish valuable data for the safety certification of PP-P8.