Biological Evaluation of Medical Devices in the Form of Suppositories for Rectal and Vaginal Use

Background. Programs of preclinical safety studies of the health care products depend on the regulatory status of the investigated products. The classification of such products, in particular suppositories for rectal and vaginal use, is a critical step of developing tactics for their biological evaluation. Adaptation of biological evaluation methods for the medical devices based on the combination of biologically active substances, as well as evaluation of the results of such studies is urgent task of biomedicine. Objective. To substantiate the regulatory status and to carry out a biological evaluation of medical devices in the form of vaginal suppositories based on octenidine dihydrochloride ("Prodexyn") and in the form of rectal suppositories based on Saw palmetto, Levisticum officinale and Calendula officinalis extracts ("Pravenor"). Methods. Biological evaluation was conducted according to the requirements of ISO 10993 standards using in vitro and in vivo biological test systems (cytotoxicity in cell culture and the MTT test, sensitizing and irritating effect in guinea pigs). Results. The cytotoxicity (СС50) of the medical device "Prodexyn" extract in Vero cell culture was 8.35 μg/ml calculated as octenidine dihydrochloride and 416.65 μg/ml calculated as dexpanthenol. "Pravenor" medical device was found to be non-toxic in Vero cell culture. According to the results of MMT assay CC50 for octenidine dihydrochloride was 1.67 μg/ml, and 83.33 μg/ml – for dexpanthenol. CC50 indicators calculated for the different active ingredients of the medical device "Pravenor" were the following: 50 mg/ml for the dwarf palm berries extract (Saw palmetto), 16.67 mg/ml for the lovage roots extract (Levisticum officinale), and 16.67 mg/ml for the calendula flowers extract (Calendula officinalis). No sensitizing or skin irritating effects were observed in guinea pigs. Conclusions. Biological evaluation of medical devices in the form of rectal suppositories "Pravenor" and vaginal suppositories "Prodexyn" performed using in vitro and in vivo biological systems. It was demonstrated an acceptable level of safety of the products. The MTT test was 5 times more sensitive than the Vero cell culture method in determination of cytotoxicity.

Radiolabeled PSMA Inhibitors

PSMA has shown to be a promising target for diagnosis and therapy (theranostics) of prostate cancer. We have reviewed developments in the field of radio- and fluorescence-guided surgery and targeted photodynamic therapy as well as multitargeting PSMA inhibitors also addressing albumin, GRPr and integrin αvβ3. An overview of the regulatory status of PSMA-targeting radiopharmaceuticals in the USA and Europe is also provided. Technical and quality aspects of PSMA-targeting radiopharmaceuticals are described and new emerging radiolabeling strategies are discussed. Furthermore, insights are given into the production, application and potential of alternatives beyond the commonly used radionuclides for radiolabeling PSMA inhibitors. An additional refinement of radiopharmaceuticals is required in order to further improve dose-limiting factors, such as nephrotoxicity and salivary gland uptake during endoradiotherapy. The improvement of patient treatment achieved by the advantageous combination of radionuclide therapy with alternative therapies is also a special focus of this review.

Clinical and Regulatory Status of Silymarin

Introduction: Silymarin is a mixture of 9 different active flavanolignans extracted from the seeds of the milk thistle (Silybum marianum) plant. It has been extensively used by local people and medicinal practitioners in European countries from around 2,000 years for the treatment of liver and biliary-related disorders. Aims of this review: This review article documents and critically assesses, for the first time, up to date the regulatory status of the silymarin extract for the treatment of hepatic and other diseases. Methods: Information was collected systematically from electronic scientific databases including Google Scholar, Science Direct, PubMed, Web of Science, ACS Publications, Elsevier, SciFinder, and Wiley Online Library, as well as other literature sources (e.g., books). Additionally, various regulatory authority websites have been searched for exploring the data. Key findings: Silymarin has been approved in different doses for the treatment or adjuvant therapy for liver disorders by the regulatory authorities of different countries. But, silymarin has still been used as a dietary supplement in the US, despite its high sales. The potential of silymarin to be approved for various other indications has been proved by assessing its efficacy in human patients. In addition to efficacy, it is found to be safe and well-tolerated. Conclusion: Phytochemical and pharmacological studies have demonstrated that silymarin is an important medicinal herb with prominent bioactivities. Thus, there is a need to conduct clinical trials in a larger number of patients to get approval for use in diseases like metabolic syndrome, diabetes mellitus, cancer, and many more.

Interest of Coffee Melanoidins as Sustainable Healthier Food Ingredients

Coffee melanoidins are generated by the Maillard reaction during the thermal processes occurring in the journey of coffee from the plant to the cup (during drying and roasting). Melanoidins, the brown pigments formed as the end products of this reaction, have been reported in cascara, silverskin, spent coffee grounds, and coffee brew. The latter is one of the main natural sources of melanoidins of the daily diet worldwide. However, their presence in coffee by-products has been recently described. These complex macromolecules possess multiple health-promoting properties, such as antioxidant, anti-inflammatory, dietary fiber effect, and prebiotic capacity, which make them very interesting from a nutritional point of view. In addition, they have a great impact on the sensory profile of foods and their acceptance by the consumers. The present study is a descriptive, narrative, mini-review about the nature, structure, digestibility, properties (sensory, nutritional, and health-promoting), safety and regulatory status of melanoidins from the coffee brew and its by-products with a special emphasis on the latter.

Synthetic nicotine has arrived

The introduction of a new product line of the popular disposable electronic cigarette brand Puffbar, advertised as containing synthetic nicotine, has drawn attention to the increasing use of synthetic nicotine in marketed products and its uncertain regulatory status. A search of the Truth Tobacco Industry Documents revealed that the industry considered using synthetic nicotine already in the 1960s, efforts that were abandoned due to high costs and insufficient purity. Recent patents revealed renewed efforts to develop more efficient strategies for the synthesis of nicotine. Nicotine exists as two stereoisomers, S-nicotine and R-nicotine. While S-nicotine is the prevalent (>99%) form of nicotine in tobacco, a market-leading form of synthetic nicotine contains both stereoisomers at equal amounts, raising concerns about inaccurate labelling and the poorly understood health effects of R-nicotine. Other manufacturers, including a leading vendor of pharmaceutical grade nicotine, developed stereospecific strategies to synthesise pure S-nicotine, now added to electronic cigarette products marketed in the USA and UK. While S-nicotine and R-nicotine can be differentiated by enantioselective High Performance Liquid Chromatography (HPLC), differentiation of synthetic (fossil-derived) from tobacco-derived S-nicotine will require development of methods to measure carbon isotope (14C or 13C) content. Vendors claim that the FDA has no authority to regulate synthetic nicotine as a tobacco product, allowing them to circumvent the premarket tobacco product application process. However, legal analysis suggests that FDA may have the authority to regulate synthetic nicotine as a drug. Alternatively, Congress needs to include nicotine from any source within the legal definition of tobacco products.

Assessing the filtration efficiency and regulatory status of N95s and nontraditional filtering face-piece respirators available during the COVID-19 pandemic

Background The COVID-19 pandemic has severely disrupted supply chains for many types of Personal Protective Equipment (PPE), particularly surgical N95 filtering facepiece respirators (FFRs; “masks”). As a consequence, an Emergency Use Authorization (EUA) from the FDA has allowed use of industrial N95 respirators and importation of N95-type masks manufactured to international standards; these include KN95 masks from China and FFP2 masks from the European Union. Methods We conducted a survey of masks in the inventory of major academic medical centers in Boston, MA to determine provenance and manufacturer or supplier. We then assembled a testing apparatus at a university laboratory and performed a modified test of filtration performance using KCl and ambient particulate matter on masks from hospital inventories; an accompanying website shows how to build and use the testing apparatus. Results Over 100 different makes and models of traditional and nontraditional filtering facepiece respirators (N95-type masks) were in the inventory of surveyed U.S. teaching hospitals as opposed to 2–5 models under normal circumstances. A substantial number of unfamiliar masks are from unknown manufacturers. Many are not correctly labelled and do not perform to accepted standards and a subset are obviously dangerous; many of these masks are likely to be counterfeit. Due to the absence of publicly available information on mask suppliers and inconsistent labeling of KN95 masks, it is difficult to distinguish between legitimate and counterfeit products. Conclusions Many FFRs available for procurement during the COVID-19 pandemic do not provide levels of fit and filtration similar to those of N95 masks and are not acceptable for use in healthcare settings. Based on these results, and in consultation with occupational health officers, we make six recommendations to assist end users in acquiring legitimate products. Institutions should always assess masks from non-traditional supply chains by checking their markings and manufacturer information against data provided by NIOSH and the latest FDA EUA Appendix A. In the absence of verifiable information on the legitimacy of mask source, institutions should consider measuring mask fit and filtration directly. We also make suggestions for regulatory agencies regarding labeling and public disclosure aimed at increasing pandemic resilience.

Qarābādhīn (Pharmacopoeia) in Greeco-Arabian era : A Historical and Regulatory Perspective

Qarābādhīn can be termed as pharmacopoeia, contains compiled form of compound formulations or recipes. Importance of Qarābādhīn gradually increased and acquired an imperative status. The history of Qarābādhīn starts from Chiron, Aesculapius, Hippocrates, Dioscorides and Galen in Greco-Roman era. Many of early and medieval Islamic and Arab physicians play vital role and immense original contribution in this discipline and authored important and essential Qarābādhīn with systemic and scientific approaches. Although some of them could not reach the present day, many of the manuscripts can be found in various libraries across the world. Since the Arab Caliphates appreciated and patronized the fields of medicine acquired from Greeks and worked for its development, this period also known as “Greco-Arabic era”. In this work the evaluation of Qarābādhīn (particularly written in Arabic or Greek language) was done in historical and regulatory perspective particularly in Greek era and later on in Medieval Islamic era. The findings of the review indicate the importance and regulatory status of Qarābādhīn and provide information about it. It can be helpful to explore Qarābādhīn and related publications of Greek and Medieval Islamic Arabic period, which gives foundations for the present-day pharmacopeias. Since these documents also take into account ethical considerations, its utility in the fields of medicine and medical ethics should be investigated.International Journal of Human and Health Sciences Vol. 05 No. 04 October’21 Page: 388-404

Considerations from the College of American Pathologists for implementation of an assay for SARS-CoV-2 testing after a change in regulatory status

The U.S. Food & Drug Administration FDA regulates the marketing of manufacturers’ in vitro diagnostic tests IVDs including assays for the detection of SARS-CoV-2. The U.S. government’s Clinical Laboratory Improvement Amendments CLIA of 1988 regulate the studies that a clinical diagnostic laboratory needs to perform for an IVD before placing it into use. Until recently, the FDA has authorized the marketing of SARS-CoV-2 IVDs exclusively through the Emergency Use Authorization EUA pathway. The regulatory landscape continues to evolve, and IVDs will eventually be required to pass through conventional non-EUA FDA review pathways once the emergency declaration is terminated in order to continue to be marketed as an IVD in the U.S. When FDA regulatory status of an IVD changes or is anticipated to change, the laboratory should review manufacturer information and previously performed internal verification studies to determine what, if any, additional studies are needed before implementing the non-EUA version of the IVD in accordance with CLIA regulations. Herein, the College of American Pathologists’ Microbiology Committee provides guidance for how to approach regulatory considerations when an IVD is converted from EUA to non-EUA status.

Food Supplementation with Vitamins and Minerals: An Overview

Vitamins are organic substances that are essential for normal metabolism, growth, development, and regulation of cell function. Mineral elements are non-organic substances. They constitute 4% of the body mass. Multivitamins and minerals are commonly used as dietary supplements to maintain good health and prevent chronic diseases. In this chapter, we described selected vitamins and minerals used as nutritional supplements. We presented their dietary sources as well as their absorption, metabolism, storage and functions in human body. We also discussed their benefits and potential harmful effects associated with deficiency or excess intake. The prevalence, recommended intakes, regulatory status and health effects of supplementation with these micronutrients were also detailed. Finally, the use of vitamins and minerals as food additives was described in this chapter.