Biosimilars in Oncology: Latest Trends and Regulatory Status.

Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.

A highly contiguous reference genome assembly for Colletotrichum falcatum pathotype Cf08 causing red rot disease in sugarcane.

Among the biotic factors, which affect the productivity and quality of sugarcane, red rot disease caused by the fungal pathogen, Colletotrichum falcatum is the most devastating that cause enormous loss to millers as well as cane growers. We present a highly contiguous genome assembly of C. falcatum pathotype Cf08 which is virulent to popular sugarcane varieties grown in more than 3 million hectares in sub-tropical India. By performing long read sequencing on PacBio RSII system, 56.06 Mb assemblies with 238 contigs having N50 of 0.51 Mb and L50 of 34 was produced. A BUSCO completeness score of 97.24% (including 4.1% fragmented) of the entire C. falcatum Cf08 nuclear genome, greatly improved contiguity compared to an existing highly fragmented draft of C. falcatum Cf671 genome (48.13 Mb) was obtained. This Cf08 assembly had 54.14% GC content and possessed < 1% repetitive elements. A total of 18,635 protein-coding genes were predicted compared with 12,270 for Cf671. Among 617 CAZymes predicted, glycoside hydrolases were the predominant (298), and among 7264 genes associated with pathogenicity/virulence, 77 genes having effector functions were identified. The assembled genome showed its similarity with the genome of C. graminicola and C. higginsianum, the causal organisms of anthracnose in maize and in members of Brassicaceae, respectively. A total of 94 large sequences (> 100 kb) of Cf08 were mapped over C. higginsianum 10 of 12 chromosomes with 106 synteny blocks. Results discussed here would provide an important tool for future studies of evolutionary and functional genomics in C. falcatum. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02695-x.

A global comparison of implementation and effectiveness of materiovigilance program: overview of regulations.

Medical devices, being life-saving tools, are considered to be a boon for healthcare system. However, in addition to their therapeutic effects, there are several ill consequences that are caused by these devices. An effective cohort vigilant system was needed to manage such adverse effects. This had led to the introduction of materiovigilance. Materiovigilance is the study and follow-up of occurrences that arise as a result from the usage of the medical equipment. It not only manages adverse events (AE) but also creates harmonization among countries. Keeping these objectives in focus, the principles, perspectives, and practices with regard to materiovigilance that are followed in the USA, Europe, China, Japan, Australia, Canada, and India are being compared. Such a comparison is essential, which will help us to understand the gaps in the current regulatory systems in the above-mentioned countries and furthermore will provide a comprehensive picture to the regulatory authorities to amend any existing laws if required. These amendments may ensure optimal patient safety by providing them a benign experience from the use of medical devices.

Advanced drug delivery approaches against periodontitis.

Periodontitis is an inflammatory disease of gums involving the degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10-15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes) in the pockets and release of toxins, enzymes and stimulation of body's immune response. Various local or systemic approaches were used for an effective treatment of periodontitis. Currently, controlled local drug delivery approach is more favorable as compared to systemic approach because it mainly focuses on improving the therapeutic outcomes by achieving factors like site-specific delivery, low dose requirement, bypass of first-pass metabolism, reduction in gastrointestinal side effects and decrease in dosing frequency. Overall it provides a safe and effective mode of treatment, which enhances patient compliance. Complete eradication of the organisms from the sites was not achieved by using various surgical and mechanical treatments. So a number of polymer-based delivery systems like fibers, films, chips, strips, microparticles, nanoparticles and nanofibers made from a variety of natural and synthetic materials have been successfully tested to deliver a variety of drugs. These systems are biocompatible and biodegradable, completely fill the pockets, and have strong retention on the target site due to excellent mucoadhesion properties. The review summarizes various available and recently developing targeted delivery devices for the treatment of periodontitis.

Development and Characterization of Novel Medicated Nanofibers Against Periodontitis.

Periodontitis is an inflammatory disease of gums involving degeneration of periodontal ligaments, creation of periodontal pocket and resorption of alveolar bone, thus disrupting the support structure of teeth causing their loosening and finally removal. Since this disease is mainly confined to the periodontal pocket, so site specific drug delivery of an antibiotic is the best suitable option. This also eradicates the demerits of oral dosing like low drug concentration reaching the target site and the various systemic side effects. In the present work, an efficient and easy technique of electrospinning has been used to develop non-woven drug loaded and biodegradable nanofiber patch with inbuilt property of high surface area to volume ratio. Hyaluronic acid (HA) has been used specifically as the polymer since it possesses remarkable properties like providing an extracellular matrix supporting tissue regeneration, anti-inflammation and mucoadhesion. A blend of this natural polymer with another polymer (Polyvinyl alcohol) has been tried since HA alone cannot be electrospun efficiently as it shows very high viscosity at very low polymer concentration. The developed formulation presented controlled release behavior with good mucoadhesive strength. The in vivo studies confirmed the maintenance of minimum inhibitory concentration (MIC) over an extended period of time in addition to a significant antiinflammatory effect. All these observations suggested that the above formulation forms a stable intra periodontal pocket drug delivery system.

Feto-maternal Outcome Using New Screening Criteria of Serum TSH for Diagnosing Hypothyroidism in Pregnancy.

INTRODUCTION: Evidence suggests that by using the classical non pregnant reference range for serum TSH (STSH), one might miss hypothyroidism in pregnancy. Therefore, upper normal cut off value of S TSH should be taken as <2.5 mIU/L in the first trimester and <3mIU/L in the second and third trimester. However, two Indian studies have reported higher trimester specific reference ranges in the Indian pregnant women. OBJECTIVES: To assess the maternal and fetal outcomes using new screening criteria with upper S TSH cut off as >3mIU/L, for diagnosing hypothyroidism in pregnancy. MATERIALS AND METHODS: This study was a cross sectional study, carried out in the Department of Obstetrics and Gynaecology of a tertiary care hospital, in collaboration with the Department of Endocrinology. Pregnant women with ≤ 20 weeks gestation, attending antenatal OPD from December 2010 to January 2012 were included in the study. On the basis of S TSH level, women were divided into Study Group with S TSH level between 3.1 to 6.2 mIU/L, (new range to be studied) and an equal number of age and parity matched Control Group with S TSH levels between 0.4 to 3 mIU/L. The maternal and fetal outcomes were compared between study and control groups. RESULTS: During the study period, a total of 66 women had S TSH between 3.1-6.2 mIU/L. Maternal and fetal outcomes in both the groups were comparable. There was no difference in the mode of delivery between study and control groups. CONCLUSION: The lower S TSH cut off recommended for diagnosing hypothyroidism in pregnancy may not be applicable to pregnant Indian women.