Review of the New Substances Notification Regulations (Organisms): Proposed approach to modernize NSNR (organisms)
Official title: Review of the New Substances Notification Regulations (Organisms): Proposed Approach to Modernize NSNR (Organisms) - Companion Document for Stakeholder Engagement 2024
1. Purpose and expected outcomes
Health Canada (HC) and Environment and Climate Change Canada (ECCC) invites comments on proposals for updating the New Substance Notification Regulations (Organisms) (NSNR (Organisms)). The NSNR (Organisms) are published under the Canadian Environmental Protection Act, 1999 (CEPA), Part 6. For more information on the Government of Canada’s New Substances (NS) program, please visit Canada.ca.
The expected outcomes of this engagement are to:
- obtain feedback on proposed approaches. The proposals address issues highlighted in the Fall 2022 Discussion Paper, based on feedback described in the ‘What We Heard’ report
- continue to enable feedback on issues related to the regulation of animate products of biotechnology (that is, living organisms)
The objective of reviewing the NSNR (Organisms) is to:
- enhance protection of human health, the environment, and biodiversity in Canada
- strengthen openness of the regulatory oversight for living organisms
- increase regulatory efficiency
- support innovation within a scientific risk-based regulatory regime
2. Background – CEPA and NSNR (Organisms) review
On April 13, 2021, the Government of Canada announced its commitment to strengthen CEPA through Bill C-28. As part of this commitment, the Government began a complete review of the NSNR (Organisms). The objective of this review was to modernize the regulatory framework for animate products of biotechnology in Canada. The Government brought back Bill C-28 as Bill S-5 (Strengthening Environmental Protection for a Healthier Canada Act) in the Senate on February 9, 2022. Bill S-5 received Royal Assent on June 13, 2023, and the current review of the NSNR (Organisms) is the next step to strengthening CEPA. For more information on Bill S-5, please visit Canada.ca.
In fall of 2022, the NS program sought public comment on how the NSNR (Organisms) should be modernized. Comments were received through virtual engagement sessions and an online public consultation platform (PlaceSpeak). People and organizations were asked to discuss their view of the regulations and if any changes should be made. A Discussion Paper was provided as part of that consultation to help respondents answer these questions. The NS program received more than 300 comments from industry, academia, the public, Indigenous organizations, and non-governmental organizations. The NS program has summarised these comments in a What We Heard report, published on October 17, 2023.
Comments received by the NS program indicate that there is:
- interest in more chances for meaningful engagement
- a need to address issues that have come about since the regulations were first published in 2005Footnote 1
- interest in exploring new and pragmatic ways to regulate living organisms
The NS program has considered these comments to inform the proposed approaches and recommendations to modernize NSNR (Organisms). These are described below in Section 4.
We still want to hear from you! We’re seeking feedback on our plans to modernize through planned engagement sessions. You can also submit comments in writing to the New Substances program inbox by July 5, 2024.
Similar to the NS program’s approach in fall 2022, this document includes questions to help guide feedback.
3. Scope of the NSNR (Organisms) review
In this phase of the NSNR (Organisms) modernization, the proposals focus on 3 key themes:
- Improving openness and transparency
- Responding to advances in science and technology
- Reducing regulatory inefficiencies
The NS program proposes both regulatory amendment(s) and non-regulatory tools (for example, guidelines) to address issues under these 3 themes. These proposals are described below in Section 4.
It is not possible to address some issues through the NSNR (Organisms) (for example, demonstration of need requirementsFootnote 2). As the Government of Canada implements the new CEPA, some issues are part of broader initiatives (for example, labelling). The NS program will work with other government departments, programs, and agencies for issues that require a “whole of government” approach. These issues are important, even if they are not part of this phase of the NSNR (Organisms) modernization.
4. Proposed approaches for the modernization of NSNR (Organisms)
A summary of the proposed approaches is provided in Annex I.
4.1 Improving openness and transparency
4.1.1 Mandatory consultations for vertebrate or prescribed organisms
Context
Bill S-5 includes 2 key amendments relevant to animate products of biotechnology:
(1) The Ministers must consult any interested persons when assessing a new living organism that is a vertebrate animal or a prescribed living organism or group of living organisms
(2) The Minister must publish a notice of waived information requirements under Part 6 of the Act as soon as possible
The NS program has heard from stakeholders that they are looking for better opportunities to engage and participate in the regulatory decision-making process for new living organisms. From a program perspective, the assessment periods for vertebrate animals or prescribed living organisms need to be long enough to allow for meaningful consultations. It would also be helpful to require certain additional information and data for notifications of new vertebrates or prescribed living organisms. This would help ensure that the consultation process is consistent. The objective would be to provide sufficient detail in notification summaries subject to consultation so that interested persons have enough scientific information to comment. It would also make the consultations more predictable for the regulated party (vis-à-vis, the notifier).
Proposed approach
Based on these considerations the program proposes to:
- extend the assessment period by an extra 60 days, via regulatory amendments, for new living organisms that are subject to mandatory consultations to facilitate a 60-day public comment period
- establish, in regulation, a requirement for notifiers of organisms subject to mandatory consultation to provide a summary of relevant information and data in a format that program can make publicly available for meaningful public engagement
- develop a template to assist notifiers in providing the summary of relevant information and data for mandatory consultations
- continue to encourage notifiers of higher organisms to participate in the voluntary public consultation process where the mandatory consultation requirements do not apply
4.2 Responding to advances in science and technology
4.2.1 Facilitating access to products of biotechnology, including biologic drugs subject to the Food and Drugs Act (FDA)
Context
Modern biotechnology has allowed researchers and developers to use living organisms in many innovative new applications. Examples include the development of vaccines, personalized medicines that can treat genetic diseases and cancer, and cell and gene therapies (CGT). Safety, efficacy and quality reviews of these products are conducted under the authority of the FDA and the Food and Drug Regulations (FDR). However, neither are listed on Schedule 4 of CEPA. Therefore, the indirect human health and environmental risks of such products are subject to CEPA and the NSNR (Organisms) before they are manufactured in or imported into Canada.
Amendments to the FDA in 2023 expanded the Minister of Health’s regulation making authority to support the environmental risk assessment and management regime for drugs. Until those regulations are finalized, amending the NSNR (Organisms) to focus on the most relevant information and data requirements for FDA biologics will help facilitate access to innovative medicines for patients. These amendments would be done in consultation with our domestic regulatory partners. Consultations with other government groups have indicated that the NS program should consider streamlining our regulatory approach to avoid duplication and alignment of timelines.
Stakeholders have expressed support for a streamlined pre-market environmental assessment regime for living organisms in biologic drugs that aligns with FDA assessment periods. The FDA provides 30 days for clinical trial applications (CTA), whereas the NSNR (Organisms) prescribes a 120 day assessment period. Stakeholders have also expressed support for avoiding regulatory duplication with other instruments, while ensuring the protection of human health in Canada and the environment.
Stakeholders have expressed concerns over Schedule 1 NSNR (Organisms) information requirements that were designed for industrial or environmental applications. These are more onerous compared to CTA requirements, and some information requirements (for example, effects on biogeochemical cycling) do not apply for biologic drugs. The NS program therefore proposes to develop a tailored set of information requirements to support assessments of potential risks from biologic drugs to the environment and indirect human health.
Proposed approach
Based on these considerations the program proposes to introduce a tiered approach based on the level of risk, noting that:
- human cells do not represent a hazard to human health in Canada or the environment and cannot survive outside of the human body
- non-replicative viruses cannot reproduce within the human body and treated individuals are unlikely to shed them, as long as the genetic modifications making them non-replicative are stable and prevent any reversion to replicative competent viruses
- large scale, commercial use of non-replicative organisms and use of replicative organisms under any setting (that is, for clinical and commercial use) may represent a higher level of risk
- administering biologic drugs in clinical settings (for example, clinical trials) represents a lower risk, given they are used in controlled settings reducing environmental releases and appropriate waste management procedures are in place
The proposed tiered approach would accordingly be the following:
- First, to exempt human cell culture therapies used in clinical trials and for commercialization from notification with certain criteria. These criteria include, for example:
- cells or cell lines cannot contain intact Risk Group (RG) 2, RG3 or RG4 human or animal pathogens that are able to produce replication competent or infectious pathogens
- cells or cell lines must be administered by competent professionals in health care settings where procedures are in place to reduce environmental releases
- Second, to introduce reduced information requirements for non-replicative viral vectors used in clinical trials that meet certain criteria. For example:
- information focussed on potential for reversion of non-replicative viruses to replicative competent viruses
- administration by competent professionals in health care settings where procedures are in place to reduce environmental releases
- Third, to create a subset of Schedule 1 requirements for the assessment of non-replicative viral vectors during large scale commercialization, and for replicative viral vectors and other organisms used under any setting
- Finally, the following timelines will be considered for biologic drugs:
- a 30-day assessment timeline for notifications for clinical trials to align with the FDA assessment timeline
- a 120-day assessment timeline for notifications (non-replicative or replicative) at the commercialization stage (current timeline for NSNR (Organisms) Schedule 1) as there is a potential for widespread release
4.3 Reducing identified inefficiencies
4.3.1 Post-assessment review of living organisms under NSNR (Organisms)
Context
CEPA is adaptive and agile to new information that becomes available following a risk assessment. This provides regulatory oversight of living organisms throughout their lifecycle.
Some stakeholders have commented that the science-based risk assessment and management regime that exists under CEPA and the NSNR (Organisms) is appropriate and effective. Others have expressed that there could be long-term irreversible environmental and human health impacts from the release of living organisms, especially genetically modified living organisms. These stakeholders have also suggested that post-assessment monitoring would capture and manage risks associated with uncertainty. Post-assessment monitoring could help demonstrate the safe use of a new living organism, especially where no history of safe use exists (that is, for “first-in-class” products).
Provisions under CEPA provide some authority to:
- gather and consider new information for previously assessed organisms
- review and update risk management measures to ensure they remain relevant and effective
- request more tests if there is reason to suspect that an organism is toxic or capable of becoming toxic
The precautionary principle also guides the NS program’s administration of CEPA and the NSNR (Organisms). This principle means that a lack of full scientific certainty should not delay cost-effective measures to prevent environmental harm. However, using existing authorities under CEPA in a proactive and predictable way would ensure that new scientific information is incorporated into the regulation of living organisms. This approach would account for any information that was not available at the time of the initial assessment.
Proposed approach
Based on these considerations, the program proposes to:
- develop and consult on a policy to prioritize organisms for review when new and relevant scientific information could change the outcome of the original risk assessment
- use a process similar to the Identification of Risk Assessment Priorities (IRAP) approach used for the review of chemicals and polymers
4.3.2 Revising the regulations for higher organisms commensurate to the level of intended release
Context
The NSNR (Organisms) has 5 Schedules that outline the information and data requirements for notification of new living organisms. 4 of these Schedules are for micro-organism notifications under various circumstances. Only one Schedule sets out the requirements for organisms other than micro-organisms (that is, higher organisms).
Under the NSNR (Organisms), the required information depends on the type of organism and the activity being conducted, as follows:
- for the import or manufacture of a microorganism anywhere in Canada, the notifier must provide information under Schedule 1
- for the import or manufacture of a microorganism in a contained facility, the notifier must provide information under Schedule 2
- for the import or manufacture of a microorganism for an experimental field study, the notifier must provide information under Schedule 3
- for the manufacture of a micro-organism at the site from which it was isolated for introduction into the same site, the notifier must provide information under Schedule 4
- for the import or manufacture of an organism other than a micro-organism, the notifier must provide information under Schedule 5
For micro-organisms, information requirements and the length of assessment periods change depending on the Schedule that the micro-organism is notified under. This approach creates regulatory requirements that are adapted to the nature and degree of potential environmental exposure. However, there is a single Schedule for the notification of higher organisms. All higher organisms are subject to the same information requirements and assessment period, regardless of the exposure during their import into or manufacture in Canada.
Feedback from regulated parties described the approach for micro-organisms is more efficient and support for adopting a similar approach for higher organisms. Some stakeholders, however, support the current uniform approach for higher organisms as it ensures the same standard for all risk assessments. These stakeholders expressed concerns about establishing regulatory requirements based on how an organism is imported or manufactured (for example, in a contained facility). They commented that this would limit the NS program’s ability to consider potential impacts on the environment and biodiversity under all circumstances, such as in the event of an accidental release. The NS program would continue to be able to ask regulated parties for any information and data needed to find potential risks to the environment and human health in Canada. This is the same power currently applied for micro-organisms.
The NS program proposes to adopt an approach for higher organisms where regulatory requirements reflect the nature and degree of possible environmental exposure. This approach would consider some of the different ways that an organism may be imported or manufactured in Canada. For example, in contained facilities, as part of experimental field studies, or in line with confinement procedures.
This approach would improve efficiency by establishing information requirements and assessment periods that are adapted to the level of intended release. This approach would aid in the detection of activity-specific risks while removing information requirements that are not relevant to the notified activity. Higher organisms that are subject to mandatory consultations would also need longer assessment timelines and a requirement to provide a summary of the notification. The NS program would use these to conduct consultations to help ensure sufficient chances for meaningful engagement in the regulatory decision-making process. These higher organisms are the vertebrate or prescribed living organisms described in section 4.1.1 of this document).
Also, the NS program proposes to amend the definition of “contained facility” in the NSNR (Organisms). The NS program would amend the definition so that notifiers would need physical and operational requirements in place that prevent the release of the organism or its biological materials. This would help implement a new Schedule for contained use that addresses stakeholder concerns regarding potential environmental impacts of higher organisms used in containment. To support regulated parties meet this requirement, the NS program would also update the NSNR (Organisms) notification guidelines. The updates would reflect domestic and internationally accepted best practices for the use of higher organisms in contained facilities.
Proposed approach
Based on these considerations, the program proposes to:
- amend the NSNR (Organisms) to include new, shorter Schedules containing information requirements tailored to the import or manufacture of:
- higher organisms in a contained facility
- higher organisms used in experimental field study
- require a subset of information for higher organisms notified under Schedule 5 for release in accordance with confinement procedures, similar to Schedule 1 for micro-organisms
- amend the assessment period length for higher organisms as follows:
- 120 calendar days for higher organisms imported/manufactured in contained facilities
- 150 calendar days for higher organisms imported/manufactured as part of an experimental field study
- 180 calendar days for higher organisms imported/manufactured anywhere in Canada (that is, as per current Schedule 5)
- amend the definition of “contained facility” to include specific consideration for higher organisms
The 2 additional proposed Schedules for organisms other than micro-organisms and their corresponding activities are outlined below:
- for the import or manufacture of an organism other than a microorganism in a contained facility, the notifier must provide information under the proposed Schedule 6
- for the import or manufacture of an organism other than a micro-organism for an experimental field study, the notifier must provide information under the proposed Schedule 7
4.3.3 Streamlining the regulatory scope for unmodified organisms
Context
CEPA and the NSNR (Organisms) regulate all new living organisms that are not in the scope of an equivalent Act or Regulation listed in Schedule 4 of CEPA. This applies regardless of whether the organism is genetically modified or not. This approach ensures that all new living organisms undergo a risk assessment before anyone imports them into or manufactures them in Canada. However, this approach also captures some unmodified organisms that is, ones that may already exist in Canada. This is because they either are already in use and/or naturally exist in the Canadian environment.
Regulated parties have raised concerns that the NSNR (Organisms) is too restrictive for some types of unmodified organisms that are already present in Canada or in the Canadian environment. This includes:
- unmodified micro-organisms that are considered low risk to public health and that are used in contained facilities
- domesticated and wild animals that can be found naturally in the Canadian environment
The NS program is considering regulated parties’ feedback. It is also considering feedback from other stakeholders that cite concerns about invasive species and potential impacts on local biodiversity. Therefore, the NS program is considering policies and changes to guidance that would streamline the notification of certain unmodified organisms that are already in Canada.
The following unmodified higher organisms would be exempt from notification under the NSNR (Organisms):
- livestock and domesticated animals
- animals in zoos, aquariums, and circuses
- and wild animals that are found naturally in the Canadian environment
Notifiers of certain unmodified micro-organisms would be able to request waivers from certain information requirements under the NSNR (Organisms). They would also be able to indicate that some information requirements are “not applicable”. These are unmodified micro-organisms with the following criteria:
- that have previously been classified as low risk to public health (that is Species classified as Risk Group 1 on Public Health Agency of Canada’s ePathogen database)
- that are isolated from the Canadian environment
- that are notified for manufacture and use within a contained facility without release
Micro-organisms that are not listed as Risk Group 1 organism on the ePathogen database would not be eligible for this proposed streamlined notification policy. This approach would help to match regulatory requirements to the risk posed by such micro-organisms. This would still fulfill CEPA’s mandate to protect the environment and human health in Canada.
In addition to these amendments, the NS program would need to clearly define terminology surrounding modified, unmodified, and naturally occurring in the context of the regulations. It would also need to provide guidance for applications of biotechnology that result in organisms that are substantially the same as organisms produced through traditional breeding practices.
Proposed approach
Based on these considerations, the program proposes the following:
- develop policy and guidance for the NSNR (Organisms) to streamline information requirements for unmodified micro-organisms that are both:
- isolated in Canada that are considered low risk human pathogens
- used only in a contained facility
- amend NSNR (Organisms) to exempt unmodified higher organisms naturally found in Canada and that are identified as “implicitly listed on the DSL” in the NSNR (Organisms) notification guidance
- define or describe key terms such as modified, unmodified, and autochthonous in the NSNR (Organisms) notification guidance
4.3.4 Addressing regulatory gaps and overlaps with Human Pathogens and Toxins Act and Regulations (HPTA)/(HPTR)
Context
The Public Health Agency of Canada’s (PHAC) Human Pathogens and Toxins Act (HPTA) and Human Pathogens and Toxins Regulations (HPTR) came into full force in December, 2015. Since then, stakeholders have found regulatory duplication for new living organisms that fall under both CEPA/NSNR (Organisms) and the HPTA/HPTR. This applies particularly for the manufacture or import of micro-organisms used in contained facilities.
However, the HPTA/HPTR only regulates:
- human pathogens that are micro-organisms
- nucleic acid or proteins listed on the HPTA Schedules 2 to 4 or that are categorized as Risk Group 2, 3 or 4
- toxins listed on the HPTA Schedule 1
PHAC regulates terrestrial animal pathogens and toxins, including those affecting birds and amphibians. However, it excludes those affecting aquatic animals and invertebrates through the Health of Animals Regulations. The HPTA/HPTR does not capture Risk Group 1 micro-organisms. For Risk Group 2, 3, or 4 human pathogens and toxins listed on Schedule 1, PHAC does not evaluate potential environmental impacts. The HPTA/HPTR does not cover activities with higher organisms. Therefore, all these cases still need regulatory oversight under the NSNR (Organisms). To streamline the regulatory process for micro-organisms that fall under the purview of both PHAC and the NS program, both groups already share relevant information. This includes:
- the risk group classification of the micro-organisms
- the adequacy of containment
- the confinement procedures for the use of micro-organisms within the scope of the notified schedule
This information sharing process is undertaken through a Memorandum of Understanding (MOU) between PHAC and the NS program. In practice, this means sharing information on regulatory and policy activities between the NS program and PHAC. This is to address questions that they could have been asked in a pre-notification consultation or through other formal communication between regulators and the regulated party. To streamline the regulation of micro-organisms used in contained facilities that PHAC licenses under the HPTA/HPTR, the NS program is proposing to formalize the MOU through new policies and changes to guidance.
Proposed approach
Based on these considerations, the program proposes the following:
First, it proposes to develop policy or guidance to provide insight into the MOU in place between PHAC and the NS program. This is to provide regulated parties with a better understanding of how information is shared between the 2 groups.
Second, it proposes to develop policy or guidance to clarify under which Schedules human and animal pathogens may be notified. For example, Risk Group (RG) 2, RG3 and RG4 pathogens cannot be notified under Schedules inherently involving environmental release (that is Schedules 3 & 4). This would apply if the release of the micro-organism would contravene the conditions of a license issued by PHAC under the HPTA/HPTR.
Third, if these organisms are used in contained facilities with a HPTA license, notifiers may request waivers for certain information requirements, such as Schedule 2 paragraph 2 (c). This would be allowed if they provide a copy of their PHAC license and description of containment level.
4.3.5 Consideration of metabolites in micro-organism risk assessments
Context
Metabolites refer to substances produced by organisms through biological and chemical reactions. The ability of an individual strain of micro-organism to produce metabolites of concern depends on many environmental and genetic factors. Metabolites produced by a micro-organism are relevant in identifying the risks posed by an organism. Metabolites include:
- the intentional product(s) of genetic modification (for example an enzyme coded by an introduced gene for use in a cleaning product)
- secondary metabolites related to its function (for example in situ production on application of the microorganism)
Many notifications under Schedule 2 of the NSNR (Organisms) pertain to organisms that notifiers use to produce bioactive (industrial or pharmaceutical) compounds. The NS program must consider these bioactive compounds in the risk assessment. Certain intentionally produced metabolites fall under the NSNR (Chemicals & Polymers) once they pass a threshold for the quantity of manufacture or of import. Those metabolites that are not in the purview of the NSNR (Chemicals & Polymers) should be captured under the NSNR (Organisms). This is to ensure that potential environmental and/or health concerns can be assessed. These include:
- metabolites that are intentionally produced by the micro-organism and that fall under the NSNR (Chemicals & Polymers) volume threshold
- metabolites of concern that are inherently produced by an organism
Currently, there is no requirement that notifiers submit information pertaining to metabolites produced by micro-organisms. NS program evaluators can request this information on an case-by-case basis. However, including a formal information requirement regarding intentional and incidental metabolites of concern would account for them consistently. This would support an enhanced and more complete risk assessment.
Proposed approach
Based on these considerations, the program proposes to:
Amend NSNR (Organisms) Schedules to include information requirements regarding intentionally produced metabolites:
- quantity/concentration produced
- disposal methods
- any other relevant information regarding other known metabolites of concern to human health or the environment
- measures to address any potential risks from metabolites produced by the organisms prior to their manufacture or import
4.3.6. Schedule 2 – NIH guidelines & inactivation procedures
Context
The NSNR (Organisms) does not prescribe data requirements to ensure that inactivation procedures for the disposal of micro-organisms are effective in preventing release from contained facilities. This can add uncertainty to risk assessment.
Additionally, the NSNR (Organisms) currently references both the United States National Institutes of Health (NIH) guidelines Appendix K – Good Large Scale Practices and the Canadian Biosafety Standards and Guidelines. These references are used in establishing physical and operational requirements for contained facilities. The US NIH guidelines for Good Large Scale Practices may allow for users of micro-organisms handle or dispose of them outside of contained facilities in small quantities. In comparison, the NSNR (Organisms) requires that organisms used in containment cannot be introduced outside of a contained facility. The NIH guidelines are also not available in French, which raises accessibility concerns. Therefore, the Canadian Biosafety Standard and Guidelines created pursuant to the Human Pathogens and Toxins Act are more appropriate for establishing requirements for contained facilities in Canada. Both the Canadian Biosafety Standards and Guidelines are currently referenced under the NSNR (Organisms).
Proposed approach
Based on these considerations, the program proposes to:
- amend the NSNR (Organisms) to require test data to demonstrate the efficacy of methods used to inactivate the micro-organisms notified under Schedule 2 of the NSNR (Organisms)
- amend the NSNR (Organisms) to require information about the treatment and disposal of waste containing the micro-organisms and the possible by-products
- remove references to the NIH guidelines from the NSNR (Organisms), instead using the Canadian Biosafety Standards and Guidelines made pursuant to the HPTA
4.3.7 Definition of Research & Development (R&D) organisms
Context
The NSNR (Organisms) provides exemptions from notification requirements for organisms used for investigation or research, provided activities minimize risk of exposure or entry into the environment. This definition does not include control organisms that are used in a research context, such as:
- organisms used as experimental controls
- organisms used for quality assurance or quality control purposes while conducting R&D activities
- Organisms used as models for studying disease
Considering the feedback that the NS program received from stakeholders on this issue during the pre-consultation, it is considering amending the definition of “R&D Organism” under the NSNR (Organisms). This would include control organisms that are used in a research context. It would also ensure that organisms which fall outside of the scope of R&D activities continue to be subject to notification. The following activities are not R&D activities and are subject to notification:
- any introduction outside a contained facility
- sale or commercial use of an organism
- industrial applications of an organism
Proposed approach
Based on these considerations, the program proposes to:
- amend the NSNR (Organisms) to change the definition of R&D organism to include control organisms used in a research context, such as:
- QA/QC organisms used in research
- organisms used as experimental control
- experimental models for studying human disease
- amend the NSNR (Organisms) guidelines to clarify what activities qualify for the R&D exemption and which are not
4.3.8 Consideration of vulnerable environments
Context
The NS program considered susceptible populations as part of the pre-consultation that was held in the Fall of 2022. As part of the implementation of Bill S-5, ongoing initiatives led by Health Canada are working on an approach for ensuring that the health of vulnerable populations is protected from toxic substances.
Feedback the NS program received suggested that this was an important issue to consider from a human health perspective. However, it also raised that there was concern about vulnerable environments, such as protected areas and species at risk.
The NS program already considers threatened species and unique and protected areas in risk assessments. The NSNR (Organisms) guidelines indicate these considerations. However, there is room to expand to other information requirements under the NSNR (Organisms). Information requirements that are related to environmental impacts and the site of import and/or manufacture would benefit from these additions.
Proposed approach
Based on these considerations, the program proposes to:
Include wording in the NSNR (Organisms) notification guidance to indicate the consideration that notifiers should give to adverse effects on threatened species and protected ecosystems. These would be added under relevant information requirements. For example, those describing the locations of import or manufacture and those identifying potential environmental impacts.
4.3.9 Somatic Cell Nuclear Transfer cloned animals
Context
The NS program considers Somatic Cell Nuclear Transfer (SCNT) cloned animals animate products of biotechnology. This is because of the application of science and engineering in their use. As such, Canada currently requires pre-import and pre-market notification and assessment for all SCNT cloned animals, their progeny and derived products. SCNT is a technique for creating viable embryos by taking the nucleus from non-reproductive body cell of the organism and replacing it with the nucleus of an egg cell. This technology is commonly used to obtain uniform genetic stocks and preserve high value livestock animals.
The government of Canada developed a scientific opinion developed in 2009 and updated it based on more recent scientific information between 2019 and 2023. It has found that cattle and swine livestock animals produced through SCNT cloning, their progeny, and their derived products are identical to cattle and swine obtained through traditional breeding. This is in terms of food and feed safety for humans and animals, and environmental impacts. The Canadian scientific opinion is aligned with opinions published by US-FDA (2008), EFSA (2008), the Japan Food Safety Commission (2009), and the New Zealand Food Safety Authority (2010). Since SCNT cattle and swine are the same as their traditionally-bred counterparts in this regard, the NS program is considering exempting these organisms from notification under the NSNR (Organisms). This exemption is in the same manner as other unmodified livestock and domesticated animals. It aligns with the policy change proposed by the Health Products and Food Branch (HPFB) of Health Canada.
Proposed approach
Based on these considerations, the program proposes to:
Exempt cattle and swine livestock animals produced through SCNT cloning. They would not need pre-import, pre-manufacturing notification and risk assessment under CEPA/NSNR (Organisms).
4.3.10 Administrative requirements for submission of notifications
Context
Administrative requirements under the NSNR (Organisms) require notifiers to submit paper copies of a notification to the NS program. However, they do not specify a format. Broadening the wording of the NSNR (Organisms) to allow submitting digital notification packages and to provide acceptable formats for paper copies would improve efficiency and reduce burden for regulated parties and the NS program.
Proposed approach
Based on these considerations, the program proposes to:
- amend the administrative requirements under the NSNR (Organisms) to allow Minister to determine how information is submitted to the NS program
- Information may be submitted digitally, or in international and North American paper sizes
5. Next steps
- The NS program will hold information session webinars and meet with stakeholders to solicit feedback on the proposed approach to resolving these identified issues
- Incorporate stakeholder feedback into the analysis of options for resolving identified issues
- Draft regulatory amendments and policies based on the revised option analysis, for further consultation with Stakeholders following CG1 publication
Annex I. Summary of stakeholder feedback and proposed approaches to resolving identified issues under the NSNR (Organisms)
Mandatory public engagement for vertebrates or prescribed organisms
What we heard
- Stakeholders were interested in improving engagement through mandatory consultation
- Suggestions included working groups, advisory councils, and early & direct consultation with the public and civil society groups
Type of proposed change: regulatory amendment, policy and guidance
Proposed approach
- Regulatory amendment and policy changes to implement mandatory engagement with interested parties as described under CEPA
- Continue to encourage participation in the voluntary public engagement initiative
- Explore other opportunities to strengthen engagement with various stakeholder sectors
Labelling of animate products of biotechnology
What we heard
- Some stakeholders felt that mandatory labelling of genetically modified organisms, particularly those in consumer products, was warranted regardless of any safety concerns
- Other stakeholders supported the current approach, whereby labels can be required in response to identified health and environmental risks
Type of proposed change: other changes
Proposed approach
- Monitor and contribute to ongoing government-wide initiatives regarding the labelling of consumer products and strengthening Canadian’s access to information regarding toxic substances
- Retain flexibility and adapt regulation and policy as needed in response to decisions made on a whole-of-government basis to ensure continued alignment with the broader regulatory framework for animate products of biotechnology
Facilitating access to products of biotechnology, including biologic drugs subject to the Food and Drugs Act (FDA)
What we heard
- Stakeholders supported aligning requirements under NSNR (Organisms) and the FDA
- Some stakeholders felt that non-cultured human cells should continue to be regulated under the NSNR (Organisms)
- Stakeholders generally supported amending the definition of micro-organisms to excluded cultured cells, VLPs, and SVPs, but felt that it was still more practical to regulate these animate products of biotechnology under the NSNR (Organisms) rather than under the NSNR (C&P)
Type of proposed change: regulatory amendment
Proposed approach
- Exempt human cell culture therapies used in clinical trials and for commercialization from notification under NSNR (Organisms)
- Exempt modified non-replicative viral vectors used in clinical trials from notification under NSNR (Organisms)
- Tailor information requirements for the assessment of other living organisms used in FDA Biologics
- Apply a 30-day assessment timeline for clinical trials to align with the FDA assessment timeline and 120 days assessment timeline for notifications at commercialization stage
Post-assessment review of living organisms
What we heard
- Some stakeholders felt that strengthening post-assessment authorities under the NSNR (Organisms) is necessary to build confidence in regulatory decisions
- Other stakeholders felt that post-assessment approaches, such as long-term environmental monitoring, should only be implemented in proportion to risk
- Some stakeholders feel that new living organisms should have demonstrable benefits in order to offset long-term risks and uncertainty
- Other stakeholders felt that the added costs introduced by a demonstration of need component would outweigh any benefits given that the health and environmental safety of a new living organism is already assessed under the current approach
Type of proposed change: policy and guidance
Proposed approach
- Implement a policy to periodically review completed assessments for organisms on the DSL and those subject to risk management measures for relevant new scientific information
- If relevant new information is identified that would justify further investigation, re-evaluate the organisms to determine if the initial risk assessment conclusion and risk management measures remain valid or should be updated
Demonstration of need for new living organisms
What we heard
- Some stakeholders feel that new living organisms should have demonstrable benefits in order to offset long-term risks and uncertainty
- Other stakeholders felt that the added costs introduced by a demonstration of need component would outweigh any benefits given that the health and environmental safety of a new living organism is already assessed under the current approach
Type of proposed change: other changes
Proposed approach
- Leverage ongoing efforts to enhance meaningful engagement and post-assessment reviews to address core concerns related to uncertainty and long-term risk mitigation
Streamlining the regulations for higher organisms commensurate to the level of intended release
What we heard
- Some stakeholders felt that the addition of new notification Schedules for higher organisms would help improve efficiency and effectiveness of the regulations for activities other than environmental release
- Other stakeholders felt that the addition of new notification Schedules could undermine considerations of environmental impacts and the consequences of accidental releases
Type of proposed change: regulatory amendment, policy and guidance
Proposed approach
- Add new Schedules to the NSNR (Organisms) for higher organisms imported/manufactured in contained facilities or as part of experimental field trials
- Incorporate existing relevant standards and guidance for the use of higher organisms in contained facilities into the NSNR (Organisms) notification guidelines
- Develop fit-to-use standards and guidelines specifically for the NSNR (Organisms), to be incorporated into the regulations at a later date
Streamlining the regulatory scope for unmodified organisms
What we heard
- Some stakeholders have indicated that the approach for regulating unmodified organisms that are found naturally in Canada is disproportionate to risk
- Other stakeholders have indicated that regulatory oversight for such organisms is still necessary given that these organisms can still pose a risk to human health in Canada and the environment
Type of proposed change: policy and guidance
Proposed approach
- Exempt unmodified higher organisms described as “implicitly listed” under the current NSNR (Organisms) notification guidelines from notification under the NSNR (Organisms)
- Develop policy and guidance for the NSNR (Organisms) to streamline information requirements for unmodified micro-organisms isolated in Canada that are considered low risk human pathogens and are used only in a contained facility
- Update the NSNR (Organisms) notification guidelines to provide clear definitions for key terms (for example unmodified, modified, autochthonous)
Addressing regulatory gaps and overlaps with the Human Pathogens and Toxins Act
What we heard
- Some stakeholders have indicated that regulatory requirements for organisms that fall under both CEPA/NSNR (Organisms) and HPTA/HPTR would benefit from streamlining to eliminate redundancies
Type of proposed change: policy and guidance, other changes
Proposed approach
- Policy/guidance to ensure regulatory alignment for the notification of Risk Group 2 (and above) human and animal pathogens that are subject to both HPTR and NSNR (Organisms)
- Explore ways to improve and formalize existing information sharing processes between the NS program and PHAC
Schedule 2 – NIH guidelines & inactivation procedures
What we heard
- Stakeholders supported the removal of references to the NIH Guidelines
- Some stakeholder felt that information on inactivation procedures was already sufficiently captured
Type of proposed change: regulatory amendment
Proposed approach
- Amend the NSNR (Organisms) to remove references to the NIH Guidelines
- Addition of information requirements for evaluating the effectiveness of inactivation procedures under Schedule 2
Consideration of metabolites in micro-organism risk assessments
What we heard
- N/A
Type of proposed change: regulatory amendment
Proposed approach
- Amend NSNR (Organisms) schedules for micro-organisms to include information requirements regarding the identification of metabolites, quantity/concentration produced, disposal methods, and any other relevant information, to address any potential risks from metabolites produced by the organisms prior to their manufacture or import
Definition of Research and Development (R&D) organisms
What we heard
- Stakeholders generally indicated that they would support the exemption of organisms used in a research context as R&D organisms
- Some stakeholders identified a need to clearly define what is and is not a “research” activity so as to ensure that the exemption for R&D organisms does not become to broad
- Stakeholders felt that the current mass and volume thresholds under the NSNR (Organisms) for R&D micro-organisms were effective and should not be changed
Type of proposed change: regulatory amendment, policy and guidance
Proposed approach
- Amend the definition of “research and development organism” under the NSNR (Organisms) to include organisms that are used in a research context
- Update guidance to clearly define what activities are considered within the scope of R&D, and what activities do not and would still require notification to the New Substances program
Consideration of vulnerable environments
What we heard
- Received feedback as part of “Vulnerable Populations” issue indicating that the NS program should make an effort to strengthen considerations for vulnerable environments (for example, protected areas and threatened species
Type of proposed change: policy and guidance
Proposed approach
- In the NSNR (Organisms) notification guidance, indicate that consideration should be given to vulnerable environments under relevant information requirements that do not already include such wording
Administrative requirements for submission of notifications
What we heard
- N/A
Type of proposed change: regulatory amendment
Proposed approach
- Amend the NSNR (Organisms) to allow for digital submission of notification packages
Somatic Cell Nuclear Transfer (SCNT) cloned animals
What we heard
- N/A
Type of proposed change: regulatory amendment
Proposed approach
- Exempt SCNT-cloned cattle and swine livestock animals from notification under the NSNR (Organisms)