An estimate of rate of deviation from NCCN guideline recommendations for central nervous system imaging in trials forming basis for drug approval in first line advanced non-small cell lung cancer (NSCLC)

Importance It is unknown whether and to what degree trials submitted to the US FDA to support drug approval adhere to NCCN guideline-recommended care in their baseline and surveillance CNS imaging protocols. Objective We sought to characterize the frequency with which the trials cited in US FDA drug approvals for first line advanced NSCLC between 2015 and 2020 deviated from NCCN guideline-recommended care for baseline and surveillance CNS imaging. Design, setting, and participants Retrospective observational analysis using publicly available data of (1) list of trials cited by the FDA in drug approvals for first line advanced NSCLC from 2015 to 2020 (2) individual trial protocols (3) published trial data and supplementary appendices (4) archived versions of the NCCN guidelines for NSCLC from 2009 to 2018 (the years during which the trials were enrolling). Main outcomes and measures Estimated percentage of trials for first line advanced NSCLC leading to FDA approval which deviated from NCCN guideline-recommended care with regards to CNS baseline and surveillance imaging. Results A total of 14 studies that had been cited in FDA drug approvals for first line advanced NSCLC met our inclusion criteria between January 1, 2015 and September 30, 2020. Of these trials, 8 (57.1%) deviated from NCCN guidelines in their baseline CNS imaging requirement. The frequency of re-assessment of CNS disease was variable amongst trials as well, with 9 (64.3%) deviating from NCCN recommendations. Conclusions and relevance The trials supporting US FDA drug approvals in first line advanced NSCLC often have CNS imaging requirements that do not adhere to NCCN guidelines. Many trials permit alternative, substandard methods and the proportion of patients undergoing each modality is uniformly not reported. Nonstandard CNS surveillance protocols are common. To best serve patients with advanced NSCLC in the US, drug approvals by the FDA must be based on trials that mirror clinical practice and have imaging requirements consistent with current US standard of care.

Study of Seroprevalence of SARS CoV2 antibodies in children in a diagnostic centre of Central India-a retrospective study

It is said that children are less affected by SARSCoV2 infection because of their young immune system, so they have relatively milder symptoms as compared to adults. So the true incidence of SARSCoV2 is not known in this age group. Serosurveys in the paediatric age group can give a much better estimate of the incidence of SARSCoV2 infection in asymptomatic and symptomatic childrenThe present study was undertaken to study the seroprevalence of SARSCoV2 antibodies in children below 18 years of age, by measuring the S1RBD domain of spike protein neutralizing IgG antibody levels.This was a retrospective study carried out from August 2020 to August 2021 in a private diagnostic centre of Central India. 539 children of both genders from newborn babies upto 18 years of age were included in the study. US FDA Emergency Use Authorized [EUA], Atellica Solution SARS-CoV-2 IgG assay that detects anti S1-RBD antibodies including neutralizing IgG against SARS-CoV-2 was used for antibody estimation. Antibody level ≥1 was termed reactive or seropositive and below 1 were considered to be non reactive or seroneagtive There were 321 males and 218 females with a male to female ratio of 1.47 :1. 57% male children were seropositive while 61.9% female children showed seropositivity with an overall positivity rate of 58.99%.The findings of our study suggest that chidren below 5 years and adolescents exhibit higher antibody responses as compared to children between 5-10 years of age. The results of our study would be of help in formulating surveillance and vaccination strategies for children and in implementing public safety guidelines.

Determination of favipiravir in human plasma using homogeneous liquid–liquid microextraction followed by HPLC/UV

Background: Favipiravir is an antiviral drug that was recently approved for the management of COVID-19 infection. Aim: This work aimed to develop a new method, using sugaring-out induced homogeneous liquid–liquid microextraction followed by HPLC/UV for the determination of favipiravir in human plasma. Materials & methods: The optimum extraction conditions were attained using 500 μl of tetrahydrofuran as an extractant and 1400 mg of fructose as a phase-separating agent. Results: The developed method was validated according to the US FDA bioanalytical guidelines and was found linear in the range of 25-80,000 ng/ml with a correlation coefficient of 0.999. Conclusion: These results showed that the developed method was simple, easy, valid and adequately sensitive for determination of favipiravir in plasma for bioequivalence studies.

Future of anti-VEGF: biosimilars and biobetters

The advent of Anti- VEGFs like Lucentis (Ranibizumab), Eylea (Aflibercept) and off-label Avastin (Bevacizumab) have radically improved visual outcomes in patients of neovascular Age Related Macular Degeneration (nARMD), Diabetic Macular Edema (DME) and Retinal Vein Occlusion (RVO). It is a matter of great concern that the US patents for Ranibizumab and Aflibercept expired in 2020 with European patents to expire in 2022 and 2025, respectively. With the expiry of these biologics, Biosimilars can prove to be saviours in the posterior segment pharmacotherapy owing to their cost effectiveness and availability of various options. Numerous biosimilars are expected to gain approval for clinical use from the US-FDA and EMA soon. Biobetters are better than the original biologic in one or more parameters but require more research and development resources. With the emergence of better manufacturing and purification processes it is imperative that the biologics and biosimilars become better. The Ophthalmologists need to have in depth knowledge about these Biosimilars and Biobetters before these molecules take over the mainstream market.

US FDA best practices for initiating early feasibility studies for neurological devices in the United States

This article describes the efforts of the US Food and Drug Administration (FDA) Office of Neurological and Physical Medicine Devices to facilitate early clinical testing of potentially beneficial neurological devices in the US. Over the past 5 years, the FDA has made significant advances to this aim by developing early feasibility study best practices and encouraging developers and innovators to initiate their clinical studies in the US. The FDA uses several regulatory approaches to help start neurological device clinical studies, such as early engagement with sponsors and developers, in-depth interaction during the FDA review phase of a regulatory submission, and provision of an FDA toolkit that reviewers can apply to the most challenging submissions.

Multi-Targeted Approaches and Drug Repurposing Reveal Possible SARS-CoV-2 Inhibitors

The COVID-19 pandemic caused by SARS-CoV-2 is unprecedented in recent memory owing to the non-stop escalation in number of infections and deaths in almost every country of the world. The lack of treatment options further worsens the scenario, thereby necessitating the exploration of already existing US FDA-approved drugs for their effectiveness against COVID-19. In the present study, we have performed virtual screening of nutraceuticals available from DrugBank against 14 SARS-CoV-2 proteins. Molecular docking identified several inhibitors, two of which, rutin and NADH, displayed strong binding affinities and inhibitory potential against SARS-CoV-2 proteins. Further normal model-based simulations were performed to gain insights into the conformational transitions in proteins induced by the drugs. The computational analysis in the present study paves the way for experimental validation and development of multi-target guided inhibitors to fight COVID-19.

Tandem Mass Spectrometry (MS/MS) in the Preclinical Pharmacokinetic Study of a Highly Prescribed SNRI Drug for Depression and Its Application to Oral Extended Release Solid Dosage Formulations in Rabbits

Preclinical pharmacokinetic (pK) studies in animal models during the formulation development phase give preliminary evidence and near clear picture of the pK behavior of drug and/or its dosage forms prior to clinical studies on humans and help in tailoring of the dosage form according to the expected and requisite clinical behavior. The present work reports first of its kind preclinical pK study on oral extended release (ER) solid dosage formulations of venlafaxine (VEN) in New Zealand White rabbits. The VEN is a highly prescribed and one of the safest and most effective therapeutic agents used in the treatment different types of depression disorders worldwide. The LC-MS/MS bioanalytical method developed for this purpose demonstrated enough reliability in simultaneously quantitating VEN and its equipotent metabolite O-desmethylvenlafaxine (ODV) in rabbit plasma. The method described uses solid phase extraction for sample preparation followed by an ultra-fast LC-MS/MS analysis. The chromatographic separation was achieved isocratically with a predominantly polar mobile phase by employing RPLC. The triple quadrupole LC/MS/MS system operated in MRM mode used an ESI probe as an ion source in positive polarity. The validation results are within the permissible limits of US FDA recommendations and acceptance criteria for bioanalytical method validation.

Vaccine Regulation, Licensing and Approval in USA

Vaccines are the foremost effective public and personal preventive health interventions, leading to vital reductions in vaccine-preventable diseases and in substantial price savings to the United States health care system. A vaccine is a biological preparation that will increase the immunity to a particular illness. Vaccine development is commonly found to be difficult and needs sharp understanding and information of recent developments by physicians and experts to confirm that safe and effective vaccines are manufactured with minimum risk. A strict regulative method to see the safety, efficacy, and quality should be achieved throughout the event of vaccine development for its authorization. The Office of Vaccines Research and Review at the CBER of the US-FDA is the federal administrative body charged with guaranteeing the safety, purity, and efficacy of vaccines within US. The licensing rules are published in the Title 21 CFR Part 60. Current authority for the regulation of vaccines is in Section 351(a) of the Public Health Service Act (PHS). Vaccine licensure, development of recommendations to be used, and implementation of these recommendations resulting in uptake, community protection, and result on illness burden represent a posh system that needs collaboration within the areas of basic science, public health, vaccine delivery and outcome observance, and public perception.

Adverse events related to unapproved stem cell products and other regenerative interventions: recommendations for more robust regulation of the direct-to-consumer marketplace

Tweetable abstract Adverse events continue to occur in the direct-to-consumer market for unapproved regenerative interventions and US FDA alone cannot adequately address the problem. Other public health strategies are needed to provide better patient protection.