Nanotechnology Responses to COVID-19.

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.

Use of a common European approach for nanomaterials' testing to support regulation: a case study on titanium and silicon dioxide representative nanomaterials.

The European Union (EU) continuously takes ensuring the safe use of manufactured nanomaterials (MNMs) in consumer products into consideration. The application of a common approach for testing MNMs, including the use of optimized protocols and methods' selection, becomes increasingly important to obtain reliable and comparable results supporting the regulatory framework. In the present study, we tested four representative MNMs, two titanium dioxides (NM100 and NM101) and two silicon dioxides (NM200 and NM203), using the EU FP7-NANoREG approach, starting from suspension and dispersion preparations, through to their characterization and final evaluation of biological effects. MNM dispersions were prepared following a refined NANOGENOTOX protocol and characterized by dynamic light scattering (DLS) in water/bovine serum albumin and in media used for in vitro testing. Potential genotoxic effects were evaluated on human bronchial BEAS-2B cells using micronucleus and Comet assays, and pro-inflammatory effects by cytokines release. Murine macrophages RAW 264.7 were used to detect potential innate immune responses using two functional endpoints (pro-inflammatory cytokines and nitric oxide [NO] production). The interaction of MNMs with RAW 264.7 cells was studied by electron microscopy. No chromosomal damage and slight DNA damage and an oxidative effect, depending on MNMs, were observed in bronchial cells. In murine macrophages, the four MNMs directly induced tumor necrosis factor α or interleukin 6 secretion, although at very low levels; lipopolysaccharide-induced NO production was significantly decreased by the titania and one silica MNM. The application of this approach for the evaluation of MNM biological effects could be useful for both regulators and industries.

Carbon Nanotubes: An Emerging Drug Delivery Carrier in Cancer Therapeutics.

BACKGROUND: The scope of nanotechnology has been extended to almost every sphere of our daily life. As a result of this, nanocarriers like Carbon Nanotubes (CNTs) are gaining considerable attention for their use in various therapeutic and diagnostic applications. OBJECTIVE: The objective of the current article is to review various important features of CNTs that make them as efficient carriers for anticancer drug delivery in cancer therapeutics. METHODS: In this review article, different works of literature are reported on various prospective applications of CNTs in the targeting of multiple kinds of cancerous cells of different organs via; the loading of various anticancer agents. RESULTS: Actually, CNTs are the 3rd allotropic type of the carbon-fullerenes that are a part of the cylindrical tubular architecture. CNTs possess some excellent physicochemical characteristics and unique structural features that provide an effective platform to deliver anticancer drugs to target specific sites for achieving a high level of therapeutic effectiveness even in cancer therapeutics. For better results, CNTs are functionalized and modified with different classes of therapeutically bioactive molecules via; the formation of stable covalent bonding or by the use of supramolecular assemblies based on the noncovalent interaction(s). In recent years, the applications of CNTs for the delivery of various kinds of anticancer drugs and targeting of tumor sites have been reported by various research groups. CONCLUSION: CNTs represent an emerging nanocarrier material for the delivery and targeting of numerous anticancer drugs in cancer therapeutics.

The Use of Montmorillonite (MMT) in Food Nanocomposites: Methods of Incorporation, Characterization of MMT/Polymer Nanocomposites and Main Consequences in the Properties.

BACKGROUND: The clay Montmorillonite (MMT) is among the nanofillers more frequently used in food packaging. The uniform dispersion of nanoparticles in polymers confers considerable improvement of mechanical, thermal, optical, and/or barrier properties in polymer/clay nanocomposites. OBJECTIVE: The aim is to ascertain the state of the art of the use of MMT for packaging purposes, with special emphasis on food applications. METHODS: A literature review was carried out through recent papers and patents that focused on the incorporation of MMT in polymers. RESULTS: This review emphasizes the interaction of MMT with polymers and their levels of incorporation in the nanocomposites. This work also highlights the analytical methodologies used for the characterization of the polymer/clay nanocomposites and the main consequences of the fillers in the properties of nanocomposites. Challenges remain about increasing the compatibility between clays and biopolymers to promote their utilization in food packaging. New strategies for immobilization of oxides, enzymes, essential oils, and other bioactive compounds are needed. CONCLUSION: MMT-based composite materials are promising to be used in intelligent and active packaging.

Machine Learning as a Proposal for a Better Application of Food Nanotechnology Regulation in the European Union.

AIMS: Given the current gaps of scientific knowledge and the need of efficient application of food law, this paper makes an analysis of principles of European food law for the appropriateness of applying biological activity Machine Learning prediction models to guarantee public safety. BACKGROUND: Cheminformatic methods are able to design and create predictive models with high rate of accuracy saving time, costs and animal sacrifice. It has been applied on different disciplines including nanotechnology. OBJECTIVE: Given the current gaps of scientific knowledge and the need of efficient application of food law, this paper makes an analysis of principles of European food law for the appropriateness of applying biological activity Machine Learning prediction models to guarantee public safety. METHODS: A systematic study of the regulation and the incorporation of predictive models of biological activity of nanomaterials was carried out through the analysis of the express nanotechnology regulation on foods, applicable in European Union. RESULTS: It is concluded Machine Learning could improve the application of nanotechnology food regulation, especially methods such as Perturbation Theory Machine Learning (PTML), given that it is aligned with principles promoted by the standards of Organization for Economic Co-operation and Development, European Union regulations and European Food Safety Authority. CONCLUSION: To our best knowledge this is the first study focused on nanotechnology food regulation and it can help to support technical European Food Safety Authority Opinions for complementary information.

Reflexões bioéticas acerca da inovação em Nanomedicamentos / Reflexiones bioéticsa acerca de la innovación en Nanomedicamentos / Bioethical Reflections on Innovation in Nanomedicines / Reflexions bioètiques sobre la innovació en nanomedicaments

A nanotecnologia vem se desenvolvendo de forma exponencial na área farmacêutica, prometendo grandes benefícios, entretanto, pode estar sujeita a riscos intrínsecos relacionados a esta ciência. Neste artigo é realizada uma reflexão acerca dos desafios enfrentados pelos órgãos regulatórios em função da ausência, ou ainda, incipiente legislação, especialmente no Brasil, visto que os documentos disponíveis em relação a regulamentação, não incluem especificações para nanomedicamentos, os quais apresentam alterações na dimensão e constituição, e consequentemente comportamento diferente de medicamentos convencionais. A contingência envolvendo o desenvolvimento de nanomedicamentos e a gestão dos riscos para a vida humana e o meio ambiente fazem com que a bioética seja invocada de forma a analisar quais os impactos decorrem deste proceso

Nanotechnology has been developing exponentially in the pharmaceutical area, promising great benefits, however, it may be subject to intrinsic risks related to this science. In this article, a reflection is made on the challenges faced by regulatory agencies due to the absence or incipient legislation, especially in Brazil, since the available documents in relation to regulation do not include specifications for nanomedicine, which present changes in the dimension and constitution, and consequently different behavior of conventional drugs. The contingency involving the development of nanomedicine and the management of the risks for human life and the environment, cause bioethics to be invoked in order to analyze the impacts of this process

La nanotecnología se está desarrollando de forma exponencial en el área farmacéutica, prometiendo grandes beneficios, sin embargo, puede estar sujeta a riesgos intrínsecos relacionados a esta ciencia. En este artículo se reflexiona sobre los desafíos enfrentados por los órganos regulatorios en función de la ausencia, o aún incipiente legislación, especialmente en Brasil, ya que los documentos disponibles en relación a la reglamentación, no incluyen especificaciones para nanomedicamentos, los cuales presentan alteraciones en la dimensión y la constitución, y consecuentemente un comportamiento diferente de los medicamentos convencionales. La contingencia que involucra el desarrollo de nanomedicamentos y la gestión de los riesgos para la vida humana y el medio ambiente hacen que la bioética sea invocada para analizar qué impactos se derivan de este proceso

La nanotecnologia s'està desenvolupant de forma exponencial en l'àrea farmacèutica, prometent grans beneficis; no obstant això, pot estar subjecta a riscos intrínsecs relacionats amb aquesta ciència. En aquest article es reflexiona sobre els desafiaments que enfronten els òrgans reguladors en funció de l'absència, o d’una legislació incipient, especialment al Brasil, ja que els documents disponibles en relació a la reglamentació no inclouen especificacions per a nanomedicaments, els quals presenten alteracions en la seva dimensió i constitució, i conseqüentment presenten un comportament diferent al dels medicaments convencionals. La contingència que involucra el desenvolupament de nanomedicaments i la gestió dels riscos per a la vida humana i el medi ambient fan que la bioètica hagi de jugar un paper a fi d’analitzar quins impactes es deriven d'aquest procés

Review of emerging concepts in nanotoxicology: opportunities and challenges for safer nanomaterial design.

Nanotoxicology and nanosafety has been a topic of intensive research for about more than 20 years. Nearly 10 000 research papers have been published on the topic, yet there exists a gap in terms of understanding and ways to harmonize nanorisk assessment. In this review, we revisit critically ignored parameters of nanoscale materials (e.g. band gap factor, phase instability and silver leaching problem, defect and instability plasmonic versus inorganic particles) versus their biological counterparts (cell batch-to-batch heterogeneity, biological barrier model design, cellular functional characteristics) which yield variability and nonuniformity in results. We also emphasize system biology approaches to integrate the high throughput screening methods coupled with in vivo and in silico modeling to ensure quality in nanosafety research. We emphasize and highlight the recommendation regarding bridging the mechanistic gaps in fundamental research and predictive biological response in nanotoxicology. The research community has to develop visions to predict the unforeseen problems that do not exist yet in context with nanotoxicity and public health hazards due to the burgeoning use of nanomaterial in consumer's product.

Insights into possibilities for grouping and read-across for nanomaterials in EU chemicals legislation.

This paper presents a comprehensive review of European Union (EU) legislation addressing the safety of chemical substances, and possibilities within each piece of legislation for applying grouping and read-across approaches for the assessment of nanomaterials (NMs). Hence, this review considers both the overarching regulation of chemical substances under REACH (Regulation (EC) No 1907/2006 on registration, evaluation, authorization, and restriction of chemicals) and CLP (Regulation (EC) No 1272/2008 on classification, labeling and packaging of substances and mixtures) and the sector-specific pieces of legislation for cosmetic, plant protection and biocidal products, and legislation addressing food, novel food, and food contact materials. The relevant supporting documents (e.g. guidance documents) regarding each piece of legislation were identified and reviewed, considering the relevant technical and scientific literature. Prospective regulatory needs for implementing grouping in the assessment of NMs were identified, and the question whether each particular piece of legislation permits the use of grouping and read-across to address information gaps was answered.

Preclinical hazard evaluation strategy for nanomedicines.

The increasing nanomedicine usage has raised concerns about their possible impact on human health. Present evaluation strategies for nanomaterials rely on a case-by-case hazard assessment. They take into account material properties, biological interactions, and toxicological responses. Authorities have also emphasized that exposure route and intended use should be considered in the safety assessment of nanotherapeutics. In contrast to an individual assessment of nanomaterial hazards, we propose in the present work a novel and unique evaluation strategy designed to uncover potential adverse effects of such materials. We specifically focus on spherical engineered nanoparticles used as parenterally administered nanomedicines. Standardized assay protocols from the US Nanotechnology Characterization Laboratory as well as the EU Nanomedicine Characterisation Laboratory can be used for experimental data generation. We focus on both cellular uptake and intracellular persistence as main indicators for nanoparticle hazard potentials. Based on existing regulatory specifications defined by authorities such as the European Medicines Agency and the United States Food and Drug Administration, we provide a robust framework for application-oriented classification paired with intuitive decision making. The Hazard Evaluation Strategy (HES) for injectable nanoparticles is a three-tiered concept covering physicochemical characterization, nanoparticle (bio)interactions, and hazard assessment. It is cost-effective and can assist in the design and optimization of nanoparticles intended for therapeutic use. Furthermore, this concept is designed to be adaptable for alternative exposure and application scenarios. To the knowledge of the authors, the HES is unique in its methodology based on exclusion criteria. It is the first hazard evaluation strategy designed for nanotherapeutics.

Nanotecnología e inseguridad jurídica: análisis de los criterios sostenidos por la Unión Europea a la luz del principio de precaución / Nanotechnology and legal insecurity: analysis of the criteria supported by the European Union in light of the precautionary principle

En estos últimos años, la Unión Europea se ha visto forzada a determinar con la máxima precisión posible cuál es el ámbito de actuación de la nanotecnología, debido a que de esta concreción depende su regulación, y por ende, uno de los principios básicos en derecho, la seguridad jurídica. Sin embargo, este incipiente proceso de normativización se está topando con innumerables problemas, debido, entre otras causas, a que los criterios empleados para acotar este campo del conocimiento, como el tamaño, el número de partículas o sus propiedades, se han seleccionado sin seguir criterios estrictamente científicos. Prueba de esta incertidumbre es que en muy poco tiempo diferentes instituciones de la UE han cambiado varias veces de criterio, reflejándose en reglamentos y directivas. Pues bien, en el presente trabajo analizamos críticamente la normativa y recomendaciones de la Unión Europea en lo referente a la nanotecnología, con objeto de mostrar los retos que presenta para la bioética a la luz del principio de precaución

In recent years, the European Union has been compelled to determine, with the highest possible accuracy, what the scope of nanotechnology is. Indeed, a clear definition is necessary in order to develop a regulatory framework that ensures legal certainty. The incipient process of regulation of nanotechnology is already facing innumerable problems, given that the criteria used to delimit its scope (such as its properties, size or numbers of particles) have been selected without following strict scientific criteria. Evidence of the current legal uncertainty is that within a short timeframe, EU institutions have used varying criteria, which has resulted in notable differences among regulations and directives. This work undertakes a critical analysis of the regulations and recommendations of the European Union on nanotechnology. Our goal is to identify the challenges that nanotechnology and its undefined scope entail for bioethics, in light of the precautionary principle

Nanotechnological Carriers for Treatment of Acne.

BACKGROUND: Acne is a multifactorial skin disease associated with pilosebaceous unit and caused by bacteria Propionibacterium acnes and Acne vulgaris. Near about 95% people throughout the world suffer from acne at some point in their life span. This disease is more prominent in adults compared to neonates and prepubescent children. Conventionally it is treated with either creams or gels having large number of side effects on patients. METHODS: We searched about recent advancements in the use of nanotechnological carriers for effective treatment of acne. We focused on the use of liposomes, niosomes, microemulsions, microsponge, microspheres, and nanoparticles to improve anti-acne therapy. Patents regarding use of nanocarrier systems to eliminate acne were also discussed in this review. RESULTS: The encapsulation of anti-acne drugs in various nanotechnological carriers improve their efficacy and reduce side effects. These carriers show controlled drug release and improved drug penetration even upto pilosebaceous unit of skin. Local tolerability of anti-acne molecules can be improved by adjusting the concentration in nanotechnological carriers. CONCLUSIONS: Nanotechnological carriers have opened a new window to design novel, effective and low dose systems for effective eradication acne disease. However, very few nanocarrier based formulations are available in market for topical use and much progress is required in this field to improve anti-acne therapy.

Criterios éticos y legales para la toma de decisiones en intervenciones relacionadas con nanotecnología / Ethical and legal criteria for decision making related to Nanotechnology

Las tecnociencias fundamentan su avance en la promesa de una mejor calidad de vida para el ser humano. Sin embargo, es necesario evitar el extremo del optimismo ignorante de los condicionantes económicos de las intervenciones tecno científicas, como también la ignorancia de las vulnerabilidades en juego. Una intervención capaz de obtener la legitimidad social implica que todos los involucrados puedan aceptar las consecuencias que se desprenden de ella. En el caso de las nanotecnologías, las intervenciones han de juzgarse según los criterios procedimentales y según la Declaración Universal de Bioética y Derechos Humanos, que al mismo tiempo podrán regir las nuevas reglamentaciones, normas y leyes que las intervenciones requieran, particularmente en previsión de sus resultados futuros personales, sociales y ambientales. (AU)

Technosciences base their innovations on the promise of a better quality of life for human beeings. However, it is essential to avoid the innocent optimism of economic conditionants of technological and scientific interventions as well as to ignore the hazards of these attempts. A socially legitimate intervention implies that every participant involved would be able to accept the consequences that derive from it. As regards to Nanotechnology, such interventions should be analyzed under the light of their procedures criteria and the Universal Declaration of Bioethics and Human Rights, that will also rule a new legislation later required for each development, forthseeing personal, social and environmental outcomes. (AU)

Methodological, political and legal issues in the assessment of the effects of nanotechnology on human health.

Engineered nanomaterials (ENMs) raise questions among the scientific community and public health authorities about their potential risks to human health. Studying a prospective cohort of workers exposed to ENMs would be considered the gold standard for identifying potential health effects of nanotechnology and confirming the 'no effect' levels derived from cellular and animal models. However, because only small, cross-sectional studies have been conducted in the past 5 years, questions remain about the health risks of ENMs. This essay addresses the scientific, methodological, political and regulatory issues that make epidemiological research in nanotechnology-exposed communities particularly complex. Scientific challenges include the array of physicochemical parameters and ENM production conditions, the lack of universally accepted definitions of ENMs and nanotechnology workers, and the lack of information about modes of action, target organs and likely dose-response functions of ENMs. Standardisation of data collection and harmonisation of research protocols are needed to eliminate misclassification of exposures and health effects. Forming ENM worker cohorts from a combination of smaller cohorts and overcoming selection bias are also challenges. National or international registries for monitoring the exposures and health of ENM workers would be helpful for epidemiological studies, but the creation of such a registry and ENM worker cohorts will require political support and dedicated funding at the national and international levels. Public authorities and health agencies should consider carrying out an ENM awareness campaign to educate and engage all stakeholders and concerned communities in discussion of such a project.

Towards a more effective and efficient governance and regulation of nanomaterials.

The uncertainty regarding the effects and risks of nanomaterials on human health and the environment, and how they should be tested and assessed in the context of current regulations, is clearly holding back the full exploitation of the innovative potential of nanomaterials. To reduce this uncertainty, the European Union funded NANoREG and ProSafe projects (jointly referred to as N1P) have made a critical evaluation of methods to test and assess these risks in the context of the current registration, evaluation, authorisation and restriction of chemicals (REACH) regulation. Where essential methods were lacking, new ones have been developed. For several existing methods, adjustments have been proposed. Possible improvements to the REACH regulation have also been identified in these projects. The results of N1P have been translated into recommendations for (European) policy makers and regulators. Part of them have a "no regret" character, meaning that the proposed actions can be considered as necessary, feasible, effective and cost efficient. The recommended measures proposed for data quality and data management will create a more solid information basis for risk assessment of nanomaterials. When implemented, the recommendations regarding REACH will improve the application of REACH in both a legal and scientific sense. In practical terms however, the application of REACH will remain complex, time-consuming and costly. Besides that, adapting and specifying the information requirements and test methods in REACH for nanomaterials that are now on the market, will not solve the regulatory hurdles for next generation (nano) materials. To better align the dynamic character of developing new materials and the static character of regulations, it is recommended to explore possibilities of a more future proof approach for securing the safety of new (nano) materials.

Régimen jurídico de la Nanomedicina en España / No disponnible

El devenir de los tiempos ha favorecido el desarrollo de tecnologías aplicadas a dispositivos, materiales, procedimientos médicos y modalidades terapéuticas desarrolladas, en algunos casos, mediante la convergencia de materiales vivos e inertes, dando lugar al descubrimiento de nuevos tratamientos médicos beneficiosos para la salud y la mejora de la calidad de vida de nuestra especie. En base a estos presupuestos metodológicos el objeto de este trabajo ha consistido en analizar cuáles son los avances más notorios que se han producido en este campo durante los últimos años y cuales es el mapa jurídico de los sistemas de Nanomedicina en un país como España inmerso, actualmente, en una desoladora época de crisis gestionada por las instancias públicas en base a recortes en el ámbito de la salud pública

The evolution has favored the development of technologies applied to devices, materials, medical procedures and therapeutic modalities developed, in some cases, by the convergence of living and inert materials, leading to the discovery of new medical treatments beneficial to health and the improvement of the quality of life of our species. Based on these methodological assumptions the objective of this work has been to analyze which are the most notorious advances that have occurred in this field during the last years and what is the legal map of the systems of Nanomedicine in a country like immersed Spain, Currently, in a bleak era of crisis managed by public bodies based on cuts in the field of public health

Returning to the Patent Landscapes for Nanotechnology: Assessing the Garden that It Has Grown Into.

The patent landscape, like a garden, can tell you much about its designers and users; their motivations, biases, and general interests. While both patent landscapes and gardens may appear to the casual observer as refined and ordered, an in-depth exploration of the terrain is likely to reveal unforeseen challenges including, for example, alien species, thickets, and trolls. As this Chapter illustrates, patent landscapes are dynamic and have been forced to continually evolve in response to technological innovation. While emerging technologies, such as biotechnology and information communication technology have challenged the traditional patent landscape, resulting in the pruning of certain elements here and there, the overarching framework and design has largely remained intact. But will this always be the case? As the field of nanotechnology continues to evolve and mature, the aim of this Chapter is to map how the technology has evolved and grown within the confines of existing structures and underlying foundation of the patent landscape and the implications thereof for the technology, industry, and the public more generally. The Chapter concludes by asking the question whether the current patent landscape will be able to withstand the ubiquitous nature of the technology, or whether nanotechnology, in combination with other emerging technologies, will be a catalyst for governments and policy makers to completely redesign the patent landscape.

Advances in Nanotechnology as They Pertain to Food and Agriculture: Benefits and Risks.

Nanotechnology is an emerging and rapidly developing toolbox that has novel and unique applications to food science and agriculture. Fast and impressive developments in nanotechnology for food and agriculture have led to new experimental prototype technologies and products. Developing various types of nanodelivery systems, detection tools, nanoscale modifications of bulk or surface properties, fabrication of wide-range bionanosensors, and biodegradable nanoplatforms can potentially improve consumer health and safety, product shelf life and stability, bioavailability, environmental sustainability, efficiency of processing and packaging, and real-time monitoring. Some recently developed nanotechnology techniques and potential product applications of nanotechnology are summarized in this review. Exposure to nanomaterials may be harmful to the consumer and the environment and might increase the potential of risk. For this reason, evaluation of the potential risks resulting from the interaction of nanomaterials with biological systems, humans, and the environment is also reviewed.

National Survey of Workplaces Handling and Manufacturing Nanomaterials, Exposure to and Health Effects of Nanomaterials, and Evaluation of Nanomaterial Safety Data Sheets.

A national survey on workplace environment nanomaterial handling and manufacturing was conducted in 2014. Workplaces relevant to nanomaterials were in the order of TiO2 (91), SiO2 (88), carbon black (84), Ag (35), Al2O3 (35), ZnO (34), Pb (33), and CeO2 (31). The survey results indicated that the number of workplaces handling or manufacturing nanomaterials was 340 (0.27% of total 126,846) workplaces. The number of nanomaterials used and products was 546 (1.60 per company) and 583 (1.71 per company), respectively. For most workplaces, the results on exposure to hazardous particulate materials, including nanomaterials, were below current OELs, yet a few workplaces were above the action level. As regards the health status of workers, 9 workers were diagnosed with a suspected respiratory occupational disease, where 7 were recommended for regular follow-up health monitoring. 125 safety data sheets (SDSs) were collected from the nanomaterial-relevant workplaces and evaluated for their completeness and reliability. Only 4 CNT SDSs (3.2%) included the term nanomaterial, while most nanomaterial SDSs were not regularly updated and lacked hazard information. When taken together, the current analysis provides valuable national-level information on the exposure and health status of workers that can guide the next policy steps for nanomaterial management in the workplace.

How to achieve safe, high-quality clinical studies with non-Medicinal Investigational Products? A practical guideline by using intra-bronchial carbon nanoparticles as case study.

BACKGROUND: Clinical studies investigating medicinal products need to comply with laws concerning good clinical practice (GCP) and good manufacturing practice (GMP) to guarantee the quality and safety of the product, to protect the health of the participating individual and to assure proper performance of the study. However, there are no specific regulations or guidelines for non-Medicinal Investigational Products (non-MIPs) such as allergens, enriched food supplements, and air pollution components. As a consequence, investigators will avoid clinical research and prefer preclinical models or in vitro testing for e.g. toxicology studies. THE AIM OF THIS ARTICLE IS TO: 1) briefly review the current guidelines and regulations for Investigational Medicinal Products; 2) present a standardised approach to ensure the quality and safety of non-MIPs in human in vivo research; and 3) discuss some lessons we have learned. METHODS AND RESULTS: We propose a practical line of approach to compose a clarifying product dossier (PD), comprising the description of the production process, the analysis of the raw and final product, toxicological studies, and a thorough risk-benefit-analysis. This is illustrated by an example from a human in vivo research model to study exposure to air pollutants, by challenging volunteers with a suspension of carbon nanoparticles (the component of ink cartridges for laser printers). CONCLUSION: With this novel risk-based approach, the members of competent authorities are provided with standardised information on the quality of the product in relation to the safety of the participants, and the scientific goal of the study.