New substances: risk assessment summary 22279

Overview

Notified organism: Alphainfluenzavirus influenzae A/Croatia/10136RV/2023 X-425A

Schedule of the New Substances Notification Regulations (Organisms) [NSNR(Organisms)]: Schedule 2 - Information Required in Respect of Micro-organisms Manufactured in or Imported to a Contained Facility That Are Not for Introduction Outside the Contained Facility or That Are for Export Only

Organism type: Virus

Use: Import and manufacture of Alphainfluenzavirus influenzae A/Croatia/10136RV/2023 X-425A for use in vaccine manufacturing

Anticipated quantity: confidential and not for disclosure

Assessment level of concern:

• Human health hazard: Low
• Human exposure: Low
• Environmental hazard: Low
• Environmental exposure: Low

Assessment conclusion under section 64 of the Canadian Environmental Protection Act, 1999 (CEPA): Low risk, not suspected to be toxic 

Category: Not eligible for addition to the Domestic Substances List

Recommended action: None

Waiver: Requested for data from tests of antibiotic susceptibility (paragraph 4(b) of Schedule 2 of the NSNR(Organisms)) under paragraph 106(8)(a) of CEPA

Synopsis

Alphainfluenzavirus influenzae A/Croatia/10136RV/2023 X-425A (hereafter, the notified organism) was notified for its import and manufacture in a single contained facility in Toronto (ON) for use in future vaccine manufacturing.

• There is no evidence to suggest a risk of adverse human health effects from the use of this organism in a contained facility
• No live organisms will be released from the facility
• There is no evidence to suggest a potential risk of adverse effects to the environment and the general population in Canada from the notified use

Owing to the low potential for hazard and the low potential for exposure to the environment and the general population in Canada, the notified organism is not suspected to meet the criteria in paragraphs 64(a), (b), or (c) of CEPA.

A waiver requested for information element 4(b) of Schedule 2 of the NSNR(Organisms) for the data from tests of antibiotic susceptibility was granted. Information gathered from such tests to determine whether the organism is susceptible to antibiotics is not necessary given that the notified organism does not carry any genes conferring antibiotic or antiviral resistance and it will be fully inactivated prior to its use in a vaccine drug product.

Background information

The notified organism is a live reassortant strain, which is a virus whose genome contains gene segments derived from two or more different parental viruses, produced through genetic reassortment. It will be manufactured in a Public Health Agency of Canada (PHAC) licensed Containment Level 2 (CL-2) facility located in Toronto (ON). It is intended to be used as a component of the vaccine product, Fluzone HD®.

Hazard

The environmental and human hazard potential of the notified organism is determined to be low because:

• the notified organism was produced by reassorting of genes from two wild type influenza A viruses to generate a high growth reassortant
• the notified organism is classified as a Risk Group 2 human and animal pathogen by PHAC, meaning it presents a low community risk but moderate individual risk
• the reassortment process leading to development of the notified organism is well-defined and stable
  • the reassorted genetic segments are not known to exhibit any pathogenic or toxic properties
  • considering the complete inactivation of the notified virus during the vaccine product development, no further reassortment with a wild type influenza virus is expected
• similar to other RNA viruses, the notified organism is expected to mutate, resulting in potential viral variants during its propagation
  • propagation of the notified strain will be limited to the minimum extent necessary for vaccine production and testing, thereby reducing its ability to mutate and create new variants
• there is no evidence to suggest that wild type influenza A viruses can infect aquatic or terrestrial plants or invertebrates
• the host range of wild type influenza A viruses is limited to humans, avian, and mammalian species
  • wild type influenza A viruses cause self-limiting infections in humans that usually resolve within a week, with outbreaks occurring seasonally in Canada
• genome analysis of the notified organism did not identify any antimicrobial or antiviral resistance genes
  • any infection will be unlikely given that the notified virus will be inactivated/killed prior to use in the vaccine product
  • nonetheless in case of infection by the notified organism, antiviral agents are available for treatment

Hazards related to micro-organisms used in the workplace should be classified accordingly under the Workplace Hazardous Materials Information System (WHMIS)^{Footnote 1} .

Exposure

The environmental and indirect human exposure potential of the notified organism is determined to be low because:

• the notified organism will be imported into and manufactured in a contained facility in Toronto (ON) in accordance with CL-2 requirements of the Canadian Biosafety Standard, 3rd edition (2022)
• other potential uses of the notified organism include its manufacture for large scale production of inactivated virus to support Canadian vaccination regimes
  • use of this inactivated virus in vaccine products is subject to the Food and Drugs Act
• prior to its use in the final vaccine product, the notified organism will be subjected to a kill step
  • inactivation methods were adequately described by the notifier
  • the final vaccine product will not contain any live viruses
• a closed system will be maintained throughout the manufacturing process.
• all personnel in the manufacturing plant have adequate training, and the standard operating procedures are in place to deal with any accidental spills or loss of strain culture
• releases of live virus into the environment are expected to be negligible since all liquid, solid, and gaseous wastes containing the notified organism will be inactivated prior to disposal or release into the environment
  • containment measures are also in place in the event of a spill
• in the unlikely event of an accidental release from the facility, similar to any wild type influenza A virus, the notified organism is not expected to persist for long in the environment outside of a mammalian host

Risk characterization

Owing to the low potential hazard and the low potential exposure, the environmental and human health risks associated with the import and manufacture of Alphainfluenzavirus influenzae A/Croatia/10136RV/2023 X-425A in a CL-2 facility is determined to be low.

Risk assessment conclusion

There is no evidence to suggest a potential risk of adverse environmental and human health effects to the environment and general population in Canada from the import and manufacture of Alphainfluenzavirus influenzae A/Croatia/10136RV/2023 X-425A in a CL-2 facility. The risk to the environment and human health associated with the import and manufacture of Alphainfluenzavirus influenzae A/Croatia/10136RV/2023 X-425A in a CL-2 facility is not suspected to meet criteria in paragraphs 64(a), (b), or (c) of CEPA. No further action is recommended.