Emerging technologies and their impact on regulatory science

There is an evolution and increasing need for the utilization of emerging cellular, molecular and in silico technologies and novel approaches for safety assessment of food, drugs, and personal care products. Convergence of these emerging technologies is also enabling rapid advances and approaches that may impact regulatory decisions and approvals. Although the development of emerging technologies may allow rapid advances in regulatory decision making, there is concern that these new technologies have not been thoroughly evaluated to determine if they are ready for regulatory application, singularly or in combinations. The magnitude of these combined technical advances may outpace the ability to assess fit for purpose and to allow routine application of these new methods for regulatory purposes. There is a need to develop strategies to evaluate the new technologies to determine which ones are ready for regulatory use. The opportunity to apply these potentially faster, more accurate, and cost-effective approaches remains an important goal to facilitate their incorporation into regulatory use. However, without a clear strategy to evaluate emerging technologies rapidly and appropriately, the value of these efforts may go unrecognized or may take longer. It is important for the regulatory science field to keep up with the research in these technically advanced areas and to understand the science behind these new approaches. The regulatory field must understand the critical quality attributes of these novel approaches and learn from each other's experience so that workforces can be trained to prepare for emerging global regulatory challenges. Moreover, it is essential that the regulatory community must work with the technology developers to harness collective capabilities towards developing a strategy for evaluation of these new and novel assessment tools

The Importance of Metrology and Standardization of Nanomaterials for Food Industry and Regulatory Authorities in Europe

From Crossref via Jisc Publications Router

New recombinant bi- and trispecific antibody derivatives

Bispecific antibodies (BsAb) are promising therapeutic tools in tomorrow's medicine. When constructing BsAbs, the final molecular size should be large enough to avoid rapid renal clearing, but small enough to allow efficient tissue distribution. In order to produce such intermediate sized BsAb, a good heterodimerisation technique will improve existing production methods. When considering recombinant expression of BsAbs, the heterodimerisation motif can be incorporated into the molecule. Recombinant BsAb can e.g. be made by fusing single chain variable fragments (scFv) to a heterodimerisation domain. We compared the efficiency of the isolated CL and CH1 constant domains with complete Fab chains to drive heterodimerisation of BsAbs in mammalian cells. We found that the isolated CL:CHI domain interaction was inefficient for secretion of heterodimers. However, when the complete Fab chains were used, secretion of a heterodimerised bispecific antibody was successful. By C-terminal fusion of scFv molecules to the Fd- and the L-chains efficient heterodimerisation in mammalian cells was obtained and a novel intermediate sized, disulfide stabilised BsAb could be efficiently produced. Since the Fab chain encodes a binding specificity on its own, bispecific (BsAb) or trispecific (TsAb) antibodies can be made. This gave rise to disulphide stabilised Fab-scFv BsAb (Bibody) or Fab-(scFv)2 TsAb (Tribody) of intermediate molecular size. Heterodimerisation of the L and Fd-containing fusion proteins was very efficient, and up to 90% of all secreted antibody fragments was in the desired heterodimerised format. All building blocks remained functional in the fusion product, and the bispecific character of the molecules as well as the functionality was demonstrated. Due to the high heterodimerisation efficiency, the ease of purification of the desired product from by-products and the lack of post-production processing, this method for producing bi- or trispecific antibodies in mammalian cells could become a method of choice for the production of intermediate sized trispecific antibodies, BsAb with monovalent or bivalent binding for one antigen, or immunoconjugates

Ecotoxicological and regulatory aspects of environmental sustainability of nanopesticides

From Elsevier via Jisc Publications RouterHistory: accepted 2020-09-28, epub 2020-10-12, issue date 2021-02-15Article version: AMPublication status: PublishedFunder: São Paulo Research Foundation; Grant(s): #2017/21004-5, #2019/20124-2Funder: CNPq; Grant(s): #427498/2018-0Funder: CESAM; Grant(s): UIDB/50017/2020, UIDP/50017/2020Funder: FEDERFunder: NANORIGO: Establishing a NANOtechnology RIsk Governance Framework; Grant(s): 814530Recent years have seen the development of various colloidal formulations of pesticides and other agrochemicals aimed at use in sustainable agriculture. These formulations include inorganic, organic or hybrid particulates, or nanocarriers composed of biodegradable polymers, that can provide a better control of the release of active ingredients. The very small particle sizes and high surface areas of nanopesticides may however also lead to some unintended (eco)toxicological effects due to the way in which they interact with the target and non-target species and the environment. The current level of knowledge on ecotoxicological effects of nanopesticides is scarce, especially in regard to the fate and behaviour of such formulations in the environment. Nanopesticides will however have to cross a stringent regulatory scrutiny before marketing in most countries for health and environmental risks under a range of regulatory frameworks that require pre-market notification, risk assessment and approval, followed by labelling, post-market monitoring and surveillance. This review provides an overview of the key regulatory and ecotoxicological aspects relating to nanopesticides that will need to be considered for environmentally-sustainable use in agriculture

Nanomaterials in Food – Current and Future Applications and Regulatory Aspects

Nanotechnology can contribute to the development of innovative applications in the agriculture, food and feed sector by e.g. enabling improved delivery of nutrients or increased efficacy of agrichemicals. It is expected that applications will increase in the near future and may therefore become a relevant source of human exposure to nanomaterials (NM). To gain more up-to date information, RIKILT and the Joint Research Centre (JRC) were commissioned by the European Food Safety Authority (EFSA) to prepare an inventory of currently used and reasonably foreseen applications of NM in agriculture and food/feed production and carried out a review of regulatory aspects concerning NM in both EU and non-EU countries. An analysis of the information records in the inventory shows that nano-encapsulates, silver and titanium dioxide are the most frequent type of NM listed and that food additives and food contact materials are the most frequent types of application. A comparison between marketed applications and those in development indicates a trend from inorganic materials (e.g. silver) towards organic materials (nano-encapsulates, nanocomposites). Applications in novel food, feed additives, biocides and pesticides are currently mostly at a developmental stage. The review of EU and non-EU legislation shows that currently a few EU legal acts incorporate a definition of a nanomaterial and specific provisions for NM, whereas in many non-EU countries a broader approach is applied, which mainly builds on guidance for industry.JRC.I.5-Systems Toxicolog

Regulatory aspects of nanotechnology in the agri/feed/food sector in EU and non-EU countries

Nanotechnology has the potential to innovate the agricultural, feed and food sectors (hereinafter referred to as agri/feed/food). Applications that are marketed already include nano-encapsulated agrochemicals or nutrients, antimicrobial nanoparticles and active and intelligent food packaging. Many nano-enabled products are currently under research and development, and may enter the market in the near future. As for any other regulated product, applicants applying for market approval have to demonstrate the safe use of such new products without posing undue safety risks to the consumer and the environment. Several countries all over the world have been active in examining the appropriateness of their regulatory frameworks for dealing with nanotechnologies. As a consequence of this, different approaches have been taken in regulating nano-based products in agri/feed/food. The EU, along with Switzerland, were identified to be the only world region where nano-specific provisions have been incorporated in existing legislation, while in other regions nanomaterials are regulated more implicitly by mainly building on guidance for industry. This paper presents an overview and discusses the state of the art of different regulatory measures for nanomaterials in agri/feed/food, including legislation and guidance for safety assessment in EU and non-EU countries.JRC.I.4-Nanobioscience