New substances: risk assessment summary 22296 and 22297

Overview

Notified organisms:

• Phage QP-STA-003 targeting Staphylococcus aureus (NSN 22296)
• Phage QP-STA-005 targeting Staphylococcus aureus (NSN 22297)

Schedule of the New Substances Notification Regulations (Organisms) [NSNR(Organisms)]: Schedule 1 - Information Required in Respect of Micro-organisms

Organism type: Bacteriophage

Use: Manufacture of QP-STA-003 and QP-STA-005 as part of the QDP-STA-005 drug product for treating S. aureus infections in humans.

Anticipated quantity: confidential and not for disclosure

Assessment level of concern:

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

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

Category: Added to the Domestic Substances List on June 3, 2026

Recommended action: None

Waiver: Requested for information elements 5(a)(i), 5(a)(ii), and 6(b) of Schedule 1 of the NSNR(Organisms), under paragraph 106(8)(a) of CEPA

Synopsis

QP-STA-003 and QP-STA-005 are unmodified, naturally occurring, lytic bacteriophages that target S. aureus. They were notified for manufacture and use in Canada for the treatment of hip or knee periprosthetic joint infections (PJI) caused by antibiotic resistant S. aureus in five patients.

Other potential uses could include their use:

• in commercial drug products to treat any S. aureus infection in humans
• in products intended for biofilm removal including wastewater treatment
• as food preservatives to prevent S. aureus contamination.

Despite the medium potential exposure of the environment to QP-STA-003 and QP-STA-005 from foreseeable potential uses, there is no evidence to suggest a potential risk of adverse effects to the environment and the general population in Canada from intended and potential uses.

Based on this assessment, QP-STA-003 and QP-STA-005 are not suspected to meet criteria in paragraphs 64(a), (b), or (c) of CEPA.

Waivers requested for information elements 5(a)(i) and 5(a)(ii) of Schedule 1 of the NSNR(Organisms) for the data from tests conducted on aquatic species and terrestrial species, respectively, were granted. Information gathered from such tests to determine whether the organisms are toxic or capable of becoming toxic on aquatic and terrestrial species is not necessary given that the notified organisms are naturally occurring, lytic bacteriophages that do not contain toxin, virulence, and antibiotic resistance genes or genes associated with temperate lifestyle (such as integrase genes) which could lead to bacterial pathogenesis.

In addition, a waiver requested for information element 6(b) of Schedule 1 of the NSNR(Organisms) for the data from tests of antibiotic susceptibility was granted. Information gathered from such tests to determine whether the organisms are susceptible to antibiotics is not necessary given that the notified organisms do not carry antiviral susceptibility or resistance genes.

Background information

QP-STA-003 and QP-STA-005 are naturally occurring (that is, not genetically modified), obligate lytic bacteriophages infecting S. aureus. They were notified for their manufacture in a single contained facility in Canada, for use as bacteriophage components of a drug product, QDP-STA-005, to treat hip or knee PJIs caused by S. aureus in five patients. Upon injection into the knee or hip joint, QP-STA-003 and QP-STA-005 are expected to target and kill S. aureus via their lytic activity, thereby controlling the bacterial infection.

Hazard assessment

The environmental and human health hazard potential of QP-STA-003 and QP-STA-005 is determined to be low because:

• the bacteriophages are naturally occurring lytic bacteriophages
  • whole genome sequence analysis confirmed the species of both bacteriophages
• data provided by the notifier indicated that the bacteriophages could infect and lyse most of the S. aureus strains tested
  • the bacteriophages’ host ranges might extend to other intra-genus members
  • it is unlikely to infect other genus members such as Streptococcus, Enterococcus, or Escherichia
• bacteriophages could potentially penetrate or interact with cells of treated patients; however, they are unlikely to infect or replicate within the cells
  • the bacteriophages are not anticipated to replicate, cause infections or any other adverse effects in terrestrial or aquatic plants, invertebrates or vertebrates, including humans
• the Public Health Agency of Canada generally considers bacteriophages as Risk Group 1 pathogens for terrestrial animals and humans, meaning they present low individual and community risk
• whole genome sequence analysis and host-specificity test results provided by the notifier also suggested that the bacteriophages are non-replicative in humans and does not have the potential to become virulent
• the bacteriophages lack the ability to integrate its genetic material into the host bacteria or to transfer it to another bacterium
  • horizontal gene transfer between the notified phages and other organisms in the environment is unlikely
• the notifier did not provide preclinical animal studies on the notified organism
  • published literature on other S. aureus phages using mice, rats and rabbit models have reported no adverse effects to treated animals
• published clinical studies with other S. aureus phages have reported only mild and clinically manageable health effects and similar health effects may be expected in patients^{Footnote 1}  treated with the bacteriophages
• currently there is no antiviral treatment available for the bacteriophages
  • QP-STA-003 and QP-STA-005 are phages lacking the capability to induce infection in both animals and humans, and adverse effects are not expected in the general population

Hazards related to micro-organisms used in the workplace should be classified accordingly under the Workplace Hazardous Materials Information System (WHMIS)^{Footnote 2} .

Exposure assessment

The indirect human exposure potential of QP-STA-003 and QP-STA-005 is determined to be low, whereas the environmental exposure potential is determined to be medium, because:

• the bacteriophages will be manufactured following a well-established phage production protocol and formulated as a drug product at the manufacturing facility and release to the environment is not expected
• the bacteriophages will be transported in a refrigerated state, in properly labelled secured containers to the clinical site the purposes of treating five patients with knee or hip PJIs.
• the bacteriophages will be administered to each patient via intra-articular injection by trained professionals under the controlled conditions at the clinical site
• the notifier indicated that materials used to dilute, transfer, or contain the bacteriophages solutions at the clinical site will be discarded as regular waste or biohazard waste
  • unused portions of the bacteriophages will be returned to the manufacturing facility where it will be autoclaved and disposed
  • the notified bacteriophages are intended only for use in five patients via injection over a limited course of treatment
  • the exposure of the environment and the general population to the bacteriophages from the notified use is expected to be negligible, if any
• in general, phages can be viable for several months to years at 4°C
  • phages are susceptible to extreme temperatures and pH in the environment and cannot replicate without their bacterial host
• potential uses of the bacteriophages could include their use as commercial drugs, food preservatives, or in biofilm-removal applications (such as wastewater treatment)
  • general population exposure remains low because phages replicate only in their host bacteria, whereas environmental exposure may increase at the point of introduction due to potential larger application volumes and localized releases
  • however, the bacteriophages are naturally occurring where their host thrives

Risk characterization

When used as notified in a medical setting, release to the environment and human exposure to the phages is not expected. The risk assessment also considered exposures due to the possibility of future commercial uses, as a commercial drug product, food preservative, or in products intended for biofilm removal including wastewater treatment. These potential uses were determined to have a low potential for exposure to humans and a medium potential for environmental exposures.

Based on the low hazard potential of the substances and the outcome of the assessment, the environmental and human health risks associated with the manufacture and use of QP-STA-003 and QP-STA-005 for their intended or potential uses is low.

Risk assessment conclusion

There is no evidence to suggest a potential risk of adverse environmental or human health effects for the environment and general population in Canada from the manufacture and the intended or potential uses of QP-STA-003 and QP-STA-005. The risk to the environment and human health associated with the bacteriophages are not suspected to meet criteria in paragraphs 64(a), (b), or (c) of CEPA. No further action is recommended.