Modernize NSNR

Mr. Michel Lortie
Manager, ECCC
Via email:  [email protected]

Re: Review of the New Substances Notification Regulations (Organisms): Proposed Approach to Modernize NSNR (Organisms). Stakeholder Engagement Document (Pre-Canada Gazette, Part I Consultation)

BIOTECanada supports the Government’s initiatives to establish a world class regulatory modernization initiative referenced by Canada’s Biomanufacturing and Life Sciences Strategy, and welcomes this early opportunity to provide the department with initial perspectives.

An effective regulatory environment is an essential driver for the introduction, acceleration, and adoption of biotechnology innovation as well as a protector of Canadian patients.  The speed at which our governments responded to the COVID-19 pandemic, whether to create and launch relief programs, simplify and shorten procurement processes or expedite clinical trials, shows us that we can and must aim higher. A high performing regulatory system is predictable, efficient, consistent and transparent, so as not to present barriers to business investment, innovation and ultimately, economic growth and values improved outcomes that benefits Canadians. A competitive regulatory system will accelerate the growth of Canadian companies and facilitate the attraction of innovation to Canada for Canadian patients. Canada’s ambition to be a world leading regulator is key, particularly as new game-changing technologies are developed, manufactured in Canada, and deployed such as mRNA, cell and gene therapies. In this context, industry strongly supports government’s regulatory ambition and corresponding work to modernize regulatory oversight, including the NSNR. Canada must implement modernized regulatory processes, aligned globally and harmonized to attract technology to Canada to ensure Canada establishes regulatory capacity to draw the next generation of technologies into use for and by Canadians.

As a guiding principle, Canada’s regulatory approach for NSNR should closely align with the US. Health Canada has been taking a leading role in many international collaboration and harmonization efforts with like-minded regulators, with requirements being similar to those implemented by other trusted regulatory authorities. The same approach should be applied to NSNR for the environmental risk evaluation of new innovative biologic therapies and vaccines.

BIOTECanada supports the Government’s proposals to exempt some human cell therapies in clinical use and commercial use as medicines in the Engagement Paper.  However, there are certain proposals in the NSNR which are out of step with the approaches used by other regulators, importantly including the US FDA, and will undermine the industry’s global competitiveness if implemented unamended.

In this context, the Canadian NSNR approach should be amended to more closely align with the US FDA regulatory approach as follows:

1. The proposed “tiered” approach of environmental evaluation and review timelines in Section 4.2.1 of the present Engagement Paper should align with the United States where such described instances are exempt from environmental assessment.
2. The use of microorganisms in a contained facility and/or clinical setting is subject to the controls set out in the Canadian Biosafety Standard and overseen by the Public Health Agency of Canada (PHAC).  An additional requirement for an environmental assessment of microorganisms presents an unnecessary additional layer of oversight which will add no additional environmental protection but will create additional work and uncertainty for biomanufacturing and clinical trials in Canada.  This disparity in regulatory requirements is a competitive disadvantage for Canada such that biomedical companies will choose to conduct clinical trials elsewhere, and /or source their product from manufacturers in other more efficient regulatory environments such as the US.  
3. CEPA’s New Substances Notification Regulations (Organisms) (SOR/2005-248) (NRNR(O)) pose an additional regulatory burden on manufacturing using organisms by requiring manufacturers to conduct an environmental assessment of microorganisms.  Importantly, the United States’ Environmental Protection Agency does not require environmental assessment of microorganisms if they comply with the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA molecules and are not defined as intergeneric microorganisms.¹ The industry strongly recommends Canada’s regulatory framework be more aligned with that used by the US EPA to enable biomanufacturing and clinical trials in Canada.
4. In the US for a Biologics License Application (BLA), if the substance comprises naturally occurring elements but has a sequence different from that of a naturally occurring substance, and when approval of the application does not significantly alter the concentration or distribution of the substance, its metabolites or degradation products in the environment, the need for an environmental assessment is categorically excluded because the products would not significantly affect the quality of the environment.² In Canada, any investigational product regulated under the Food and Drug Regulations Division 5 is reviewed for benefit: risk and safety as part of a Clinical Trial Application (CTA). Use in the specific clinical trial is evaluated by Health Canada. As a risk assessment is already performed in the context of the clinical trial, there should be no additional risk assessments for unmodified living organisms for clinical trials.  Development of provisions for review of biologics solely by Health Canada without an additional review by ECCC is highly encouraged, given the amendments made to the FD&A in 2023 expanding the regulation making authority for FDA biologics. Regardless of proposed streamlining of requirements and shortened timelines, any additional review by ECCC results in additional regulatory burden.

(An addendum is attached to this letter with additional specific recommendations for consideration.)

Recommendations:

• Canada’s regulatory system should be aligned with other jurisdictions (particularly the US EPA). 
• The Canadian government should take steps to reduce regulatory burden and overlap of the Canadian Environmental Protection Act (CEPA) and related regulations to facilitate the use of microorganisms in clinical trials and within contained biomanufacturing facilities.

The industry recognizes and supports the important role of Health Canada and Environment and Climate Control Canada in the health of Canadians and the environment.  Accordingly, the industry has indicated it is prepared to work collaboratively and constructively with the government on its health and environment policy agendas.   Ultimately, real and effective consultation and dialogue will be critical to the health, economic and social objectives that the government has identified for the advancement of advanced biotechnology products.

Sincerely,
Andrew Casey
President & CEO

Reference:

1. United States Environmental Protection Agency. 2012. Microbial Products of Biotechnology – Summary of Regulations under the Toxic Substances Control Act. July 10, 2019. < https://www.epa.gov/sites/production/files/2015-08/documents/biotech_fact_sheet.pdf>
2. https://www.fda.gov/media/91425/download