TRAAC framework for regulatory acceptance and wider usability of tools and methods for safe innovation and sustainability of manufactured nanomaterials

There has been an unprecedented use of advanced materials, particularly manufactured nanomaterials, in industrial applications and consumer products across several sectors in the last two decades. It has instigated concerns about the sustainability, in particular, risks and uncertainties regarding the interactions of the manufactured nanomaterials with humans and the environment. Consequently, significant resources in Europe and beyond have been invested into the development of tools and methods to support risk mitigation and risk management, and thus facilitate the research and innovation process of the manufactured nanomaterials. The level of risk analysis is increasing, including assessment of socio-economic impacts, and sustainability aspects, moving from a conventional risk-based approach to a wider safety-and-sustainability-by-design perspective. Despite these efforts on tools and methods development, the level of awareness and use of the majority of such tools and methods by stakeholders is limited. Issues of user-friendliness, trust, implementation training, regulatory or authority compliance needs, regulatory acceptance and unsuitability to the users’ needs are some of the factors which have been traditionally known to hinder their widespread use. Therefore, a framework is presented to quantify the readiness of different tools and methods towards their wider regulatory acceptance and downstream use by different stakeholders. The framework diagnoses barriers which hinder regulatory acceptance and wider usability of a tool/method based on their Transparency, Reliability, Accessibility, Applicability and Completeness (TRAAC framework). Each TRAAC pillar consists of criteria which help in evaluating the overall quality of the tools and methods for their (i) compatibility with regulatory frameworks and, (ii) usefulness and usability for end-users, through a calculated TRAAC score based on the assessment. Fourteen tools and methods were assessed using the TRAAC framework as proof-of-concept. The results provide insights into any gaps, opportunities, and challenges in the context of each of the 5 pillars of the TRAAC framework.

Research on the development of alternatives to animal testing for pharmaceutical products and international standardisation

Scientists are working to develop new and innovative alternatives to animal testing that don't rely on the use of animals. Takao Ashikaga, Hajime Kojima and Yoko Hirabayashi are part of JaCVAM which works to promote the use of alternatives to animal testing. The goal is to replace, reduce or refine (3Rs) the use of animal under International harmonization. Hirabayashi is also the representative of a research group that is funded by the AMED and the representative of a research group funded by the MHLW. A challenge the researchers are facing in their quest to ensure the welfare of experimental animals and also ensure the safety of various pharmaceutical and chemicals is the lack of biomarkers to more accurately predict toxicity for regulatory acceptance. This means that without animal testing more costly and complex non-animal methods are required and presents a barrier to the adoption of non-animal methods for international standerisation. As such, there is a need to develop an easy way to obtain a lot of information. Hirabayashi and the team are working on the development of AI that can be used to evaluate the safety of different compounds. The researchers are developing in vitro assays such as ordinary 2-dimensional culture, 3-dimensional culture including organoids or spheroids, reporter gene assay and organ-on-a chip; and in silico assays such as computer toxicology using QSAR and Read Across. The researchers hope that their innovative work will contribute to the 3Rs, benefiting animal welfare for regulatory use.

Evaluation of Drug Release from Carboxymethyl Starch-Xanthan Gum-HPMC Matrix

The use of hydrophilic polymers from natural origin. Especially the polysaccharides have been the focus of current research activity in the design of matrix device due to their non toxic, biocompatible, biodegradable nature and broad regulatory acceptance. A large number of polysaccharides such as Carboxymethyl starch, Xanthan gum, Hydroxy propyl methyl cellulose (HPMC), Sodium Alginate etc, have been used as hydrophilic matrices to investigate release behavior of drug. In order to enrich the resources, there is a quest for new polysaccharide owing to their diverse chemical composition and functional groups are amenable to chemical modification and thus tailor made polymeric matrices are obtained which which can be used to modulate oral drug release. The objective of the study is to characterize Verapamil hydrochloride loaded matrix dosage form using hydroxy propyl methyl cellulose (HPMC), xanthan gum, corn starch as rate retarding polymer. Dosage forms were prepared using different polymers along with drug Verapamil hydrochloride. Carboxymethylation was performed. Drug release was evaluated in simulated gastric media. Addition of xanthan gum significantly retarded the burse release of drug. The retardation of drug release was found to be dependent upon the concentration. The formulation composed of HPMC K4M and CS (ARI-ARI3) followed super case transport is swelling controlled, purely relaxation controlled drug delivery. Keywords: Verapamil HCl, Natural gums, xanthan gum, HPMC, sustained release

Regulatory procedures for emergency approval of medical products by regulatory agencies

Emergency use authorization of medical products by the regulatory agencies is not a usual procedure; it happens to cope with unanticipated health emergencies affecting a large group of population, these can be because of outbreak agents like virus, bacteria, etc., which can cause contagious diseases. Contagious diseases are classified into an outbreak, epidemic and pandemic disease, based on size and intensity of spread of the disease. Epidemic and Pandemic disease conditions such as CoVID-19 will trigger the emergency use authorization of products that help in the control, prevention and/or cure for the disease. EMA and FDA are well known advanced regulatory bodies, with eminent procedures for approval of the medication, harmonization of the standards as per the global regulatory acceptance. However, there are some differences between the two, in case of initiating the procedure, timelines, data required for approval of products under the emergency use. This article focuses on emergency approval of medications, regulations involved in the approval of medications and vaccines by EMA and FDA, some of the important data companies or sponsors need to submit to the regulatory bodies for approval, verification procedure and timelines for evaluation of manufacturer submitted data. Mutual recognition agreement and timeline of Remdesivir for approval by EC and FDA.

Evaluation of three rapid lateral flow antigen detection tests for the diagnosis of SARS-CoV-2 infection

IntroductionThe COVID-19 pandemic has led to high demand of diagnostic tools. Rapid antigen detection tests have been developed and many have received regulatory acceptance such as CE IVD or FDA markings. Their performance needs to be carefully assessed.Materials and Methods158 positive and 40 negative retrospective samples collected in saline and analyzed by a laboratory-developed RT-PCR test were used to evaluate Sofia (Quidel), Standard Q (SD Biosensor), and Panbio™ (Abbott) rapid antigen detection tests (RADTs). A subset of the specimens was subjected to virus culture.ResultsThe specificity of all RADTs was 100% and the sensitivity and percent agreement was 80% and 85% for Sofia, 81% and 85% for Standard Q, and 83% and 86% for Panbio™, respectively. All three RADTs evaluated in this study reached a more than 90% sensitivity for samples with a high viral load as estimated from the low Ct values in the reference RT-PCR. Virus culture was successful in 80% of specimens with a Ct value <25.ConclusionsAs expected, the RADTs were less sensitive than RT-PCR. However, they benefit from the speed and ease of testing, and lower price as compared to RT-PCR. Repeated testing in appropriate settings may improve the overall performance.

Standardisation needs for organ on chip devices

Standards can demonstrate technological and biological relevance, increase industry implementation and support regulatory acceptance. This article will give you an overview on the state of play and future needs in standardisation for OoC.

The Application, Challenges, and Advancement Toward Regulatory Acceptance of Digital Toxicologic Pathology: Results of the 7th ESTP International Expert Workshop (September 20-21, 2019)

With advancements in whole slide imaging technology and improved understanding of the features of pathologist workstations required for digital slide evaluation, many institutions are investigating broad digital pathology adoption. The benefits of digital pathology evaluation include remote access to study or diagnostic case materials and integration of analysis and reporting tools. Diagnosis based on whole slide images is established in human medical pathology, and the use of digital pathology in toxicologic pathology is increasing. However, there has not been broad adoption in toxicologic pathology, particularly in the context of regulatory studies, due to lack of precedence. To address this topic, as well as practical aspects, the European Society of Toxicologic Pathology coordinated an expert international workshop to assess current applications and challenges and outline a set of minimal requirements needed to gain future regulatory acceptance for the use of digital toxicologic pathology workflows in research and development, so that toxicologic pathologists can benefit from digital slide technology.