Beginning November 2, 2020, following the next release of the International Uniform Chemical Information Database (IUCLID), companies will be required to provide a name for the nanoforms or sets of nanoforms of their substance when registering nanomaterials under the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation. According to an item in the European Chemicals Agency’s (ECHA) September 30, 2020, weekly news, companies that have already registered their nanoforms do not need to take any immediate action, but will be required to provide a name in the next update of their registration dossier. ECHA states that a new registration manual will be available in October 2020 with advice on preparing registration dossiers that cover nanoforms. ECHA’s website includes guidance and support on nanomaterials under REACH and questions and answers on registering nanoforms.
On September 17, 2020, the European Alliance for Access to Safe Medicines (EAASM) announced the availability of a report entitled Patient Safety and Nanomedicines: The need for a centralised regulatory procedure. According to EAASM, “[n]anomedicines and their follow-on products, also referred to as nanosimilars, are complex molecules and so regulatory oversight must be scientifically fit for purpose.” The report makes three key recommendations intended to ensure patient safety and enable the European Union (EU) to harness fully the potential of this technology:
- Developing a scientific consensus on definitions for nanomedicines in Europe, improving education and fostering awareness on the complexity and sophistication of nanomedicines among policy makers, prescribers, payers, and patients;
- Adopting a European Medicines Agency (EMA) centralized procedure for all nanomedicines and nanosimilars that would ensure greater scrutiny of these complex products; and
- Clarifying regulatory criteria for the approval of follow-on/nanosimilar medicines. As manufacturing exact replicas of nanomedicines is not achievable, therapeutic similarity will need to be shown through clinical evidence. In addition, the highest possible manufacturing standards must be guaranteed and included in the license application.
EAASM states that with the upcoming EU Pharmaceutical and Industrial Strategies, “it is the right time to set the scene for building a pan-European medical agency consensus so that regulatory weaknesses can be addressed through a robust regulatory pathway and thus provide medicines with the highest quality, safety and efficacy profiles to European patients.” This applies not only to existing medicines but also to “the plethora of new medicines that are in the pipeline.” The report calls upon the European Commission’s (EC) Directorate-General for Health and Food Safety (DG SANTE), EMA, and Member States’ health authorities and regulatory bodies to address unmet medical needs and enhance quality, safety, and efficacy of nanomedicines and nanosimilars by addressing patient safety issues due to significant regulatory challenges across Europe.
On September 17, 2020, the U.S. Environmental Protection Agency (EPA) published final significant new use rules (SNUR) under the Toxic Substances Control Act (TSCA) for chemical substances that were the subject of premanufacture notices (PMN) and are subject to Orders issued by EPA pursuant to TSCA. 85 Fed. Reg. 57968. The SNURs require persons who intend to manufacture (defined by statute to include import) or process any of these chemical substances for an activity that is proposed as a significant new use to notify EPA at least 90 days before commencing that activity. The final SNURs include one for carbon nanotubes (generic) (PMN P-15-54). The SNUR requirements do not apply to quantities of the PMN substance that have been embedded or incorporated into a polymer matrix that itself has been reacted (cured) or embedded in a permanent solid polymer form that is not intended to undergo further processing, except mechanical processing. The significant new uses are:
- Workplace protection. Requirements as specified in Section 721.63(a)(1), (2)(i) and (ii), and (3) through (6), and (c). When determining which persons are reasonably likely to be exposed as required for Section 721.63(a)(1) and (4), engineering control measures (g., enclosure or confinement of the operation, general and local ventilation) or administrative control measures (e.g., workplace policies and procedures) shall be considered and implemented to prevent exposure, where feasible. For purposes of Section 721.63(a)(5), respirators must provide a National Institute for Occupational Safety and Health (NIOSH) assigned protection factor (APF) of at least 50. For purposes of Section 721.63(a)(6), particulate (including solids or liquid droplets).
- Industrial, commercial, and consumer activities. Requirements as specified in Section 721.80(k) (chemical intermediate to manufacture functionalized carbon nanotubes by oxidation with nitric acid; additive in rubber polymers to improve mechanical/physical/chemical/electrical properties; additive in resin polymers to improve mechanical/physical/chemical/electrical properties; additive in metals to improve electrical/thermal properties; additive in ceramics to improve mechanical/electrical/thermal properties; semi-conductor, conductive, or resistive element in electronic circuitry and devices; electric collector element or electrode in energy devices; photoelectric or thermoelectric conversion elements in energy devices; catalyst support element or catalytic electrode for use in energy devices; additive for transparency and conductivity in electronic devices; and electro-mechanical element in actuator, sensor, or switching devices).
- Disposal. Requirements as specified in Section 721.85(a)(1) and (2), (b)(1) and (2), and (c)(1) and (2).
- Release to water. Requirements as specified in Section 721.90(a)(1), (b)(1), and (c)(1).
The National Science Foundation (NSF) announced on August 24, 2020, that it will invest a total of $84 million over five years in a renewal of the National Nanotechnology Coordinated Infrastructure (NNCI). According to NSF, “NNCI’s 16 sites and coordinating office provide researchers from academia, large and small businesses, and government with access to leading-edge fabrication and characterization tools, instrumentation, and expertise across all disciplines of nanoscale science, engineering and technology.” NSF states that NNCI sites are in 15 states and involve 26 university and partner institutions. The new NSF awards range from $600,000 to $1.5 million per year for up to five years. The NNCI coordinating office, operated by Georgia Tech, will continue to provide users with a unified entry point to the network’s overall capabilities, as well as tools and instrumentation. The office also shares best practices for national education and outreach programs across sites. The awards include:
- Center for Nanoscale Systems, Harvard University;
- Cornell NanoScale Science and Technology Facility, Cornell University;
- KY Multiscale, University of Louisville with partner University of Kentucky;
- Mid-Atlantic Nanotechnology Hub, University of Pennsylvania with partner Community College of Philadelphia;
- Midwest Nano Infrastructure Corridor, University of Minnesota Twin Cities;
- Montana Nanotechnology Facility, Montana State University with partner Carleton College;
- nano@stanford, Stanford University;
- Nanotechnology Collaborative Infrastructure Southwest, Arizona State University with partner Northern Arizona University;
- Nebraska Nanoscale Facility, University of Nebraska-Lincoln;
- Northwest Nanotechnology Infrastructure, University of Washington with partner Oregon State University;
- North Carolina Research Triangle Nanotechnology Network, North Carolina State University with partners Duke University and University of North Carolina at Chapel Hill;
- San Diego Nanotechnology Infrastructure, University California San Diego;
- Soft Hybrid Nanotechnology Experimental Resource, Northwestern University with partner University of Chicago;
- Southeastern Nanotechnology Infrastructure Corridor, Georgia Tech with partners North Carolina Agricultural and Technical State University and University of North Carolina at Greensboro;
- Texas Nanofabrication Facility, University of Texas at Austin; and
- Virginia Tech National Center for Earth and Environmental Nanotechnology Infrastructure, Virginia Polytechnic Institute and State University.
On September 15, 2020, the European Food Safety Authority (EFSA) called for grant proposals on the use of new approach methodologies (NAM) for the hazard assessment of cellulose nanofibers. EFSA states that the use of cellulose at the nanoscale is increasing and requires an assessment. According to EFSA, the main concern is that the nanoscale characteristics (e.g., length/shape of the fibers) may influence the toxicokinetic and hazardous properties of cellulose nanofibers. The main objective of the call is to design and conduct a set of NAM-based studies for addressing the current data gaps and to offer a proposal for including the results in the regulatory hazard assessment of nanocellulose for consumers exposed via food. The studies should cover the three main areas identified by EFSA:
- Digestion or degradation, including surface modifications, of nanocellulose by the human microbiome;
- Assessment of nanocellulose uptake in human intestinal epithelia; and
- Assessment of local effects, including inflammation, of nanocellulose on the gastrointestinal epithelia.
All studies should be designed using NAMs, avoiding in vivo animal studies, and should specifically address the nanoscale properties. EFSA states that the studies should also be designed for maximizing the use of the results in the regulatory context, including internal validation protocols and a detailed level of reporting, including access to the raw data for the verification of the results during the regulatory assessment. The call includes two lots, and applicants may apply to one or both lots:
- Lot 1 covers the adaptation and use of human cellular models and in vitro microbial gastrointestinal tract (GIT) digestion systems; and
- Lot 2 focuses on the use of gut-on-a-chip models replicating GIT motility.
The call is restricted to the list of competent organizations established by EFSA’s Management Board. Proposals are due November 3, 2020. ECHA expects to notify applicants of the outcome of the call in December 2020.
This week’s All Things Chemical™ Podcast will be of interest to readers of the Nano and Other Emerging Chemical Technologies Blog. A brief description of the episode written by Lynn L. Bergeson is below.
This week I sat down with Vincent Caprio, Founder and Executive Director of the NanoBusiness Commercialization Association (NanoBCA). Vince has been on the forefront of nano innovations and optimizing opportunities for businesses to commercialize their nano creations for more than two decades. In founding the NanoBCA, Vince has placed it at the center of nanotechnology commercialization, national policy, law, and business since the beginning of the public’s focus on nanotechnology. NanoBCA has provided a much-needed spotlight on how nanotechnology has been a critical driver for the development of advanced materials, smart technology, innovations in chemistry, and a diverse range of other initiatives that have greatly benefited many economic sectors of the economy. As Chair of the Environment, Health, and Safety (EHS) Committee of the NanoBCA, I have long admired Vince’s vision, organization-building skills, and his seemingly endless list of contacts — there is no one in Washington, D.C., or elsewhere, whom Vince does not know!
In our conversation, Vince shares a bit about the early days of nanotechnology, how NanoBCA helped frame critical EHS issues in a way that moved the technology forward, his relationship with and deep engagement in the activities of the National Nanotechnology Initiative (NNI), his engagement with key Senators and Representatives on nano matters, and what’s next for nanotechnology after the 2020 elections.
ALL MATERIALS IN THIS PODCAST ARE PROVIDED SOLELY FOR INFORMATIONAL AND ENTERTAINMENT PURPOSES. THE MATERIALS ARE NOT INTENDED TO CONSTITUTE LEGAL ADVICE OR THE PROVISION OF LEGAL SERVICES. ALL LEGAL QUESTIONS SHOULD BE ANSWERED DIRECTLY BY A LICENSED ATTORNEY PRACTICING IN THE APPLICABLE AREA OF LAW.
According to the Summer 2020 edition of the National Nanotechnology Coordination Office (NNCO) Quarterly Newsletter, the 2020-2021 National Nanotechnology Initiative (NNI) nanomaterial environmental, health, and safety (nanoEHS) webinars will begin in November 2020. According to the Newsletter, the Nanotechnology Environmental and Health Implications (NEHI) Working Group is planning nanoEHS webinars to present progress in the following areas: nanomaterial measurement infrastructure; human exposure assessment; human health; environment; risk assessment and risk management methods; and informatics and modeling. The Newsletter notes that these are the research areas identified in the NNI Environmental, Health, and Safety Research Strategy (NNI EHS Research Strategy). The inaugural webinar will provide an overview of the research environment when the NNI EHS Research Strategy was developed, the major questions posed, and how collaborations and networks created a research infrastructure to address these questions. NNI will post more information at https://www.nano.gov/publicwebinars as it becomes available.
The European Chemicals Agency (ECHA) has posted the German Federal Institute for Occupational Safety and Health’s (BAuA) substance evaluation conclusion document for multi-walled carbon nanotubes (MWCNT), synthetic graphite in tubular shape and tangled. The conclusion provides a summary of how the information on the substance can be used for the purposes of regulatory risk management.
Concern(s) Subject to Evaluation
MWCNTs were originally selected for substance evaluation to clarify concerns about:
- Wide spread use;
- Consumer use;
- Discrepancy in self-classification between different registrants of the joint submission(s);
- Differences in physico-chemical properties that affect toxicity, e., number of different registered nanoforms and the choice of representative test material(s);
- Suspected specific target organ toxicity – repeat exposure (STOT RE) (differing no observed adverse effect levels (NOAEL)/no observed adverse effect concentrations (NOAEC) in several animal studies using different forms of the same test material);
- Suspected carcinogen;
- Effects on environmental organisms;
- Suspected environmental exposure;
- Cumulative exposure; and
- Suspected persistency.
During the evaluation, BAuA identified further concerns for most of the examined Human Health (HH) endpoints, precluding final conclusions with regard to the hazard assessment of the substance.
Overview of Other Processes/EU Legislation
There are no other ongoing or concluded processes at the EU level for the registered substance. In 2019, the German Competent Authority (DE-CA) submitted to ECHA a harmonized classification and labeling (CLH) proposal for rigid MWCNT with World Health Organization (WHO) fiber dimensions.
Conclusion of Substance Evaluation
The evaluation of the available information on the substance has led Germany to the following conclusions, as summarized in the table below.
According to the report, in the framework of the substance evaluation, it was not possible to resolve the concerns described above. The report states that based on ambiguities regarding the registered nanoforms, as well as based on the late updates of some of the dossiers at the very final stage of the substance evaluation, “it does not seem expedient to conclude on the substance evaluation with a decision on data requests at the present time.”
The report notes that as of January 1, 2020, companies must provide more information on nanomaterials on the European Union (EU) market under the updated Annexes to the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) regulation. In BAuA’s opinion, “these information requirements were not (adequately) addressed by the registrants yet. Thus, further action is needed.”
According to the report, BAuA currently considers it necessary for ECHA to examine first if all information according to REACH Annex VI are available within the framework of a compliance check. If information is missing, these data should be requested by respective decisions. Once all data are available, it has to be decided if further information is needed to clarify a remaining concern and if this should be requested in the framework of a compliance check or a substance evaluation.
Apart from potential requests as consequences of a compliance check, the report urges registrants to update their dossiers and/or develop testing proposals to adhere to REACH requirements.
|Need for follow-up regulatory action at EU level|
|Harmonized Classification and Labeling|
|Identification as Substance of Very High Concern (SVHC) (authorization)|
|Other EU-wide measures|
|Currently no need for regulatory risk management follow-up action at EU level; outcome of compliance check needs to be awaited first|
Currently No Follow-Up Foreseen at EU Level
Not possible for the time being. Compliance check is needed first.
Tentative Plan for Follow-Up Actions (If Necessary)
|Follow-Up Action||Date for Intention||Actor|
|Compliance check||To be determined (TBD)||ECHA|
|Potential inclusion to the Community Rolling Action Plan (CoRAP) for resuming substance evaluation||TBD||DE-CA|
According to the report, the need for a re-opening of the substance evaluation process will be determined based on the outcome of the new information generated via the Compliance Check procedure.
On August 31, 2020, the European Union (EU) Observatory for Nanomaterials (EUON) published a Nanopinion entitled “Nanosilver in healthcare — does the silver bullet exist?” by Dr. Dorota Napierska, Chemicals Policy and Projects Officer, Health Care Without Harm Europe (HCWH Europe). Napierska examines how beneficial the properties of nanosilver are in clinical settings and the risks involved. Napierska notes that a key point in assessing the toxicity of nanosilver is to adopt toxicological standardized assessment methods that are suitable for nanomaterials. According to Napierska, “there are still significant uncertainties regarding required environmental risk assessment for nanomaterials.” Napierska states that “[t]the nanotechnologies used in healthcare products need to be evaluated not only for their initial antiviral activity but also for their durability under conditions of use and how well they stand up to repeated cleaning and disinfection (i.e. assessed for leaching potential).” Napierska urges that the application and commercialization of silver-related products and technologies be “critically reassessed for both safety and necessity.”
The U.S. Environmental Protection Agency (EPA) announced on August 27, 2020, that it submitted an information collection request (ICR), “Chemical-Specific Rules under the Toxic Substances Control Act Section 8(a); Certain Nanoscale Materials” to the Office of Management and Budget (OMB) for review and approval in accordance with the Paperwork Reduction Act (PRA). 85 Fed. Reg. 52995. The ICR covers reporting and recordkeeping requirements for persons who manufacture or process chemical substances as nanoscale materials. Under Section 8(a) of the Toxic Substances Control Act (TSCA), EPA requires reporting and recordkeeping for certain chemical substances as nanoscale materials. Persons who manufacture or process these nanoscale materials must notify EPA of certain information, including production volume, methods of manufacture and processing, exposure and release information, and available health and safety information. EPA states that the reporting of these activities will provide it “with an opportunity to evaluate the information and consider appropriate action under TSCA to reduce any risk to human health or the environment.” EPA will use the reported information to inform its assessments of new chemical nanoscale materials submitted under TSCA Section 5. EPA proposes to extend the ICR, which is currently approved through August 31, 2020. Public comments were previously requested via the Federal Register on January 28, 2020, during a 60-day comment period. Comments are due September 28, 2020.
According to the notice, the entities potentially affected by this ICR are nanomaterial manufacturers and nanomaterial processors. EPA estimates that there will be 285 respondents per year and that the total estimated burden is 40,089 hours per year. EPA states that there is a decrease of 106,766 hours in the total estimated respondent burden compared with the ICR currently approved by OMB. According to EPA, the decrease reflects its expectation of decreased submissions. In the previous ICR period, the rule required an initial one-time reporting on current nanomaterials, while the reporting covered in this period requires only the reporting of new nanomaterials. EPA notes that furthermore, the burden estimates assume that the same manufacturers will report each year and, therefore, will have already undertaken rule familiarization in the previous ICR period. More information on EPA’s TSCA Section 8(a) rule is available in our January 12, 2017, memorandum, “EPA Promulgates Final TSCA Reporting and Recordkeeping Rule for Nanoscale Materials.”