What are NAMs?
NAMs (New approach methodologies) can be defined as a number of alternative methods to assess the hazard of chemical substances and drug active substances which implies the reduction of animal testing. NAMs includes “in silico” approaches, “in chemico” and “in vitro” assays, as well as the inclusion of information from the exposure of chemicals in the context of hazard assessment. They also include a variety of new testing tools, such as “high-throughput screening” and “high-content methods” e.g. genomics, proteomics, metabolomics; as well as some “conventional” methods that aim to improve understanding of toxic effects, either through improving toxicokinetic or toxicodynamic knowledge for substances.
Is there still the need to reduce animal testing?
Yes, Sure! The 3Rs Principle (Reducion, Replacement, Refinement) is still under implementation. It was firstly discussed in 1959 in USA and later developed in order to improve animal welfare during experimental studies and, at the same time and most importantly, to decrease such use. In the latter 20-30 years many alternative methods has been set up and now regularly used in the evaluation of hazardous properties of chemical substances and drug active substances. They include the “in vitro” studies and lastly the “in silico” approach where the relationship between the chemical structure of a substance and possible adverse effects (toxicological and eco-toxicological end-points) is studied.
Are there regulations including NAMs approaches considered alternative to the traditional approach)?
In April 19-26, 2016 the European Chemical Agency (ECHA) organized the workshop “New Approach Methodologies in Regulatory Science” where the importance of such approaches, advantages and how to adopt it in the frame of the safety assessment were discussed. The REACH annexes were amended in 2016 and 2017 to require companies to use NAMs for certain endpoints under certain conditions. Following these amendments, the use of non-animal tests have tripled for skin corrosion/irritation, quadrupled for serious eye damage/eye irritation, and increased more than 20-fold for skin sensitization (ECHA, 2020 reported).
REACH registration implications
Before registrants conduct higher-tier tests for assessing the safety of chemicals they import or manufacture, Article 40 of REACH requires that they submit details on their testing plans to ECHA. In that submission, companies must detail how they considered NAMs before proposing an animal test. ECHA must agree on these proposals before a company can conduct a new animal test under Annex IX or X. ECHA may reject, accept, or modify the proposed test. As required by REACH, all testing proposals involving testing on vertebrate animals are published on ECHA’s website to allow citizens and organizations the opportunity to provide information and studies about the substance in question. ECHA will inform the company that submitted the testing proposal of the Member State Committee’s decision and is required to take into account all studies and scientifically valid information submitted as part of the third-party consultation when making its decision.
Are NAMs applicable in other sectors (i.e. Pharma, Food)?
The answer is yes! NAMs are methods that applies during the evaluation of chemical hazardous properties of a chemical. Therefore can be easily used in the pharma sector in different applications such as PDE evaluation, OEL/OEB determination, Extractable and Leachables (E&L) toxicological evaluation and so on. In the food area they may be useful to determin the toxicological profile of food components and/or addititives.
Who can use/handle NAMs approach properly?
NAMs are not simple! They are composed by complex flow charts where a number of relevant information are requested to get a suitable and usable result. Robust data research can be required to start the evaluation as well as good practice with read-across, QSARs and family approaches. The capacity to judge the real need to go with animal studies is needed as well.
Chemsafe experts are deeply involved in NAMs application in various areas of activity. In case of needs, do not hesitate to contact us at chemsafe@chemsafe-consulting.com.
