New substances: risk assessment summary 22354, 22355, 22356 and 22357

Overview

Notified organisms:

• Phage QP-PSA-001 targeting Pseudomonas aeruginosa (NSN 22354)
• Phage QP-PSA-002 targeting Pseudomonas aeruginosa (NSN 22355)
• Phage QP-PSA-017 targeting Pseudomonas aeruginosa (NSN 22356)
• Phage QP-PSA-018 targeting Pseudomonas aeruginosa (NSN 22357)

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

Organism type: Bacteriophage

Use: Manufacture and use of QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 as components of the DP-QB-PSA-020 drug product for treating a multidrug resistant P. aeruginosa pulmonary infection in one patient

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), 6(b), and 6(c) of Schedule 1 of the NSNR(Organisms) under paragraph 106(8)(a) of CEPA

Synopsis

QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 are unmodified, naturally occurring, lytic bacteriophages that target P. aeruginosa. They were notified for manufacture and use in Canada for the treatment of a pulmonary infection caused by multi-drug resistant P. aeruginosa in one patient.

Potential uses could include future use:

• in commercial drug products to treat any P. aeruginosa infection in humans
• in products intended for P. aeruginosa biofilm removal with applications in wastewater treatment

QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 were determined to have a low hazard potential for the environment and human health. Despite the medium potential exposure of the environment to QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 from potential uses, there is no evidence to suggest a potential risk of adverse effects to the environment or to the health of the general population in Canada from intended and potential uses.

Based on this assessment, QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 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.

Lastly, a waiver requested for information element 6(c) of Schedule 1 of the NSNR(Organisms) for the data from tests of pathogenicity that are valid for related micro-organisms that are pathogenic to humans was granted. Information gathered from such tests to determine whether the organisms are pathogenic to humans is not necessary given that the notified organisms do not contain any genes associated with toxin production, antibiotic resistance or genes associated with a temperate lifestyle which is generally linked to the expression of bacterial virulence genes.

Background information

QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 are naturally occurring (that is, not genetically modified), obligate lytic bacteriophages infecting P. aeruginosa. They were notified for its manufacture in a single contained facility in Canada to treat a pulmonary infection caused by multidrug resistant P. aeruginosa in one patient. Upon administration, QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 are expected to target and kill P. aeruginosa via their lytic activity, thereby controlling the bacterial infection.

Hazard assessment

The environmental and human health hazard potential of QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 is determined to be low because:

• the bacteriophages are naturally occurring lytic bacteriophages
  • their identities were substantiated by the analysis of their genome sequences
• the test results provided by the notifier confirmed that the bacteriophages are lytic and capable of lysing strains of P. aeruginosa tested
  • they may infect other Pseudomonas species, but are unlikely to infect bacteria belonging to other genera
• interactions between bacteriophages and eukaryotic cells in treated patients may trigger inflammatory responses^{Footnote 1} due to the direct and repeated administration over the course of many days
  • due to their bacterial host specificity, the bacteriophages are not anticipated to cause infections or any other adverse effects in terrestrial or aquatic plants, invertebrates or vertebrates, including humans
• the bacteriophages are predicted to be non-transducing phages lacking the ability to integrate their genetic material into the genome of host bacteria, or to package bacterial genes for use in the phages themself or to transfer them to other bacteria
  • this non-transducing feature limits its involvement in phage-mediated horizontal gene transfer
• 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
  • the bacteriophages' genome analyses provided by the notifier as well as those done by by the New Substances program showed that they do not carry genes encoding toxins or conferring antibiotic resistance
• no study reports are available for human clinical studies using the bacteriophages
  • information on surrogate lytic P. aeruginosa phages provided by the notifier, and published information on other clinical uses of P. aeruginosa targeting phages, did not indicate serious side effects in bacteriophage-treated patients
• currently there are no antiviral treatments available against the bacteriophages
  • they lack the capability to cause infection in 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 health exposure potential of QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 is determined to be low, whereas the environmental exposure potential is determined to be medium, because:

• the bacteriophages have been stored by the notifier
  • they were notified as being manufactured in a facility following a previously assessed phage production protocol and then formulated as a drug product
  • protocols are in place to limit release to the environment from the manufacturing facility
• the bacteriophages will be manufactured and subsequently transported in a refrigerated state, and in properly labelled secured containers, to the clinical site for the purposes of treating one patient with a multidrug resistant P. aeruginosa pulmonary infection
• the bacteriophages will be administered to the patient by trained professionals under controlled conditions at the clinical site
• the notifier indicated that materials used to dilute, transfer, or contain the bacteriophages at the clinical site will be discarded as per their disposal procedures
  • unused portions of the bacteriophages will be returned to the notifier’s facility, where they will be autoclaved prior to appropriate disposal
  • since the bacteriophages are intended only for use in one patient over a limited course of treatment, their exposure to the environment and to the general population from the notified use is not expected
• phages are sensitive to extreme environmental temperatures and pH, and they are unable to replicate without their bacterial host
• potential uses for the bacteriophages could include their use as commercial drug products or incorporation into biofilm removal products (e.g., wastewater treatment)
  • general population exposure is expected to remain low because phages replicate only in their specific bacterial host
  • environmental exposure may temporarily increase at the point of application due to larger use volumes and localized releases
  • as the bacteriophages are naturally occurring wherever their host is present, their concentrations are expected to return to background levels over time

Risk characterization

When used as notified in a clinical setting, release to the environment and broad human exposure to the phages are not expected. The risk assessment also considered potential exposures due to the applications in commercial drug products or in products intended for biofilm removal such as those used in wastewater treatment. These potential uses were determined to pose a low potential for human exposure and a medium potential for localized environmental exposures due to release.

Based on the outcome of this assessment, including the low hazard potential of the organisms, the environmental and human health risks associated with the manufacture and use of QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018 for their intended or potential uses are considered to be low.

Risk assessment conclusion

There is no evidence to suggest a potential risk of adverse environmental or human health effects on the general population in Canada as a result of the manufacture and the intended or potential uses of QP-PSA-001, QP-PSA-002, QP-PSA-017, and QP-PSA-018. The risk to the environment and human health associated with the bacteriophages is not suspected to meet criteria in paragraphs 64(a), (b), or (c) of CEPA. No further action is recommended.