Scientific Research Policy for Human Pathogens and Toxins

Table of Contents

• 1.0 Effective Date
• 2.0 Policy Statement
• 3.0 Policy Objective
• 4.0 Authorities
• 5.0 Scope
• 6.0 Issue Analysis
• 7.0 Roles and Responsibilities
  • 7.1 Regulated Party
  • 7.2 PHAC
• 8.0 Review
• 9.0 Contact
• Appendix A: Glossary
• Appendix B: Examples of Activities that Meet or Do Not Meet the Definition of Scientific Research

1.0 Effective Date

This policy was approved on April 19, 2021 by the Director General for the Centre for Biosecurity of the Public Health Agency of Canada (PHAC). This policy is effective upon approval.

2.0 Policy Statement

This policy provides guidance on the definition of scientific research as it pertains to controlled activities under the Human Pathogens and Toxins Act (HPTA) to clarify when a Plan for Administrative Oversight (PAO) is required.

3.0 Policy Objective

HPTA stakeholders and regulated parties have been vigilant in submitting PAOs to PHAC based on their interpretation of the definition of scientific research outlined in the Human Pathogens and Toxins Regulations (HPTR). However, with a lack of formalized guidance, there has been an inadvertent submission of unnecessary PAOs from organisations whose regulated activities do not meet the intent of the HPTR requirement. This policy seeks to clarify when a party regulated under the HPTA is undertaking scientific research that would require submission of a PAO for approval along with the licence application, as set out in the HPTR.

4.0 Authorities

Section 18 of the HPTA provides the Minister of Health with the authority to issue a licence that authorizes any controlled activity in any facility if the Minister is of the opinion that the conduct of the controlled activity in the facility poses no undue risk to the health or safety of the public.

Section 3 of the HPTR states that if the applicant for a licence is a person who intends to carry out scientific research, the Minister must, before issuing a licence, determine that the person has developed a plan that sets out the administrative measures for managing and controlling biosafety and biosecurity risks during the period in which the licence is in effect.

5.0 Scope

The policy applies only to those regulated parties under the HPTA undertaking scientific research as defined by the HPTR and further elucidated in this document.

6.0 Issue Analysis

The Government of Canada developed and implemented the HPTA and HPTR to establish a safety and security regime to protect the health and safety of the public against the risked posed by human pathogens and toxins. The HPTA and HPTR apply to all organizations conducting controlled activities with human pathogens or toxins, which can include a wide range of sectors, including but not limited to: hospitals, academia, private industry, and other government departments.

During the development of the proposed policy elements for the regulatory framework for human pathogens and toxins, the Government of Canada strove to balance the need for commensurate oversight mechanisms to protect public health without overly impeding on innovation.  A risk mitigation approach was developed to balance the public health and safety concerns with the importance of promoting important and innovative Canadian research with human pathogens and toxins. All  licensed facilities are required, by the HPTA and supporting licence conditions, to have action plans in place to mitigate potential risks for exposure to human pathogens and toxins (biosafety programs) and action plans for emergency redress (biosecurity programs).

PHAC acknowledges that the activities within the research sector in particular pose unique risk factors that other sectors (e.g., diagnostics or standardized private industry production) normally do not. These factors include but are not limited to: autonomous research and researchers, perceived diffuse accountabilities, and complex reporting and governance structures.

The overall risk management framework and supporting governance structures used by research institutions may or may not be in place, or take into consideration the risks posed by human pathogens and toxins. To this end, section 3 of the HPTR requires that PHAC verify the existence of a Risk Management Plan developed by the regulated party that summarizes the biosafety and biosecurity programs that are in place prior to issuing a licence to an organization conducting scientific research.

The PAO is a high level plan, completed by the regulated party conducting scientific research, which provides an overview of the mechanisms that are in place in an institution or organization to administratively manage and control biosafety and biosecurity risks. The PAO is submitted to PHAC and satisfies the requirement of a Risk Management Plan. The PAO is intended to facilitate the development of internal accountability structures or support accountability structures that currently exist by bridging gaps in the oversight of pathogens and toxins at an institutional level.

The Organisation for Economic Co-operation and Development (OECD), in their Guidelines for Collecting and Reporting Data on Research and Experimental Development, defined scientific research and this definition was incorporated in the HPTR^Reference 1. As per Section 1 of the HPTR, scientific research means the following types of systematic investigation or research, carried out in a field of science or technology by means of controlled activities:

1. “basic research, when the controlled activities are conducted for the advancement of scientific knowledge without a specific practical application” (e.g., genomic studies to improve knowledge about disease resistance);
2. “applied research, when the controlled activities are conducted for the advancement of scientific knowledge with a specific practical application” (e.g., the development of vaccine strains to prevent disease), and;
3. “experimental development, when the controlled activities are conducted to achieve scientific or technological advancement for the purpose of creating new — or improving existing — materials, products, processes or devices” (e.g., Modifying pathways in various strains of micro-organisms to improve ethanol production). 

In keeping with the OECD interpretation, identified elements of scientific research include novelty, creativity, or uncertainty of outcome.^Reference 1 Although these core elements contribute to new discoveries that advance science and are necessary to innovation, they also bring with them a certain unpredictability and risks. Scientific research using one or more of these elements may present a heightened risk or challenge to public health. These elements can be further defined as follows:^Reference 1

1. Novelty: Research activities are usually aimed at finding new advancement in knowledge. The resulting knowledge is new and different from anything seen or known before. Novel ideas open new dimensions of reality and give new ways of practice that were not present before.
2. Creativity: Scientific research creativity involves challenging what is already known by asking "what if" questions, proposing alternative solutions, and looking across disciplinary boundaries to answer questions. Research scientists think of new ways to approach problems and questions, figure out how to collect meaningful data, and explore what those data could mean.
3. Uncertainty of outcome:  The very nature of research is characterized by uncertainty as researchers are attempting to extend the boundaries of knowledge. In many cases, prediction of outcomes can be made (educated guesses) but the study of living organisms can sometimes yield unexpected results. Often those unexpected results are the foundation of new knowledge and are of great value.

In recognition of the purpose behind the HPTR (section 3) obligation, one or more of these elements must apply to the intended scientific research to necessitate submission of a PAO by a regulated party. See Appendix B for examples of research which do and do not necessitate submission of a PAO. PHAC will assess and review the PAO to determine if appropriate mechanisms are in place in the institution or organization to administratively manage and control biosafety and biosecurity risks prior to licence issuance.

7.0 Roles and Responsibilities

7.1 Regulated Party:

Regulated parties intending to conduct controlled activities under the HPTA as well as scientific research (as defined in the HPTR and further elucidated in this policy) using human pathogens and/or toxins, are to develop and submit a PAO prior to undertaking the intended activity. The PAO provides an overview of the mechanisms in place to administratively manage and control biosafety and biosecurity risks.

7.2 PHAC:

PHAC will review and accept or reject the PAO based on scientific principles, as outlined in the Plan for Administrative Oversight for Pathogens and Toxins in a Research Setting-Required Elements and Guidance^Reference 1

8.0 Review

This policy will be reviewed on an ad hoc basis, as required.

9.0 Contact

Should you have any questions about this policy, please contact us at biosafety.biosecurite@phac-aspc.gc.ca.

Appendix A: Glossary

Term	Definition
Biosafety	The containment principles, technologies and practices used to prevent unintentional exposure to or accidental release of pathogens and toxins.
Biosecurity	The institutional and personal security measures used to prevent loss, theft, misuse, diversion or intentional release of pathogens, toxins, and other related assets.
Controlled activity	An activity referred to in subsection 7(1) of the Human Pathogens and Toxins Act: possessing, handling or using a human pathogen or toxin; producing a human pathogen or toxin; storing a human pathogen or toxin; permitting any person access to a human pathogen or toxin; transferring a human pathogen or toxin; importing or exporting a human pathogen or toxin; releasing or otherwise abandoning a human pathogen or toxin; or disposing of a human pathogen or toxin
Pathogen	A microorganism, nucleic acid or protein capable of causing disease or infection in humans or animals. They range from common bacteria like Salmonella to viruses of significant public health concern like Ebola. The HPTA defines them specifically as: a micro-organism, nucleic acid or protein that (a) is listed in any of Schedules 2 to 4 or in Part 2 of Schedule 5; or (b) is not listed in any of the Schedules but falls into Risk Group 2, Risk Group 3 or Risk Group 4.
Plan for Administrative Oversight	A high level plan which provides an overview of the mechanisms that are in place in an institution or organization to administratively manage and control biosafety and biosecurity risks.
Toxin	A biological toxin is a poisonous substance produced or derived from a microorganism that can cause adverse health effects in humans or animals, such as botulinum neurotoxin and anthrax toxin. The HPTA defines them specifically as: a substance that is listed in Schedule 1 or in Part 1 of Schedule 5.

Appendix B: Examples of Activities that Meet or Do Not Meet the Definition of Scientific Research

Notes:

The examples illustrated below are not exhaustive. They are a set of selected examples to help guide regulated parties in determining whether it is necessary to submit a PAO to PHAC.

The following types of products are specifically excluded from the HPTA overall:

1. Pathogens and toxins in their naturally-occurring environment as long as they have not been intentionally cultivated or extracted, when either in, on, or expelled from a human, cadaver, body part, or human remains; or
2. A drug in dosage form authorized under the Food and Drugs Act.

The following types of activities are exempted from requiring a licence under the HPTA, although persons conducting them are still required to satisfy the requirement to take reasonable precautions to protect the health and safety of the public against the risks posed by that activity:

1. Activities regulated by the Transportation of Dangerous Goods Act, 1992;
2. Export of human pathogens and toxins under the Export and Import Permits Act;
3. Diagnostic activities for some microorganisms, when there is either no production or – if production occurs - it is confined within a sealed container; or
4. Diagnostic activities for Risk Group (RG) 2 pathogens in a registered veterinary laboratory when such analysis is required for the care of an animal.

Part 1: Activities that meet the definition

Part 1- Activities That Meet the Definition of Scientific Research and Require Submission of a PAO
Activities	Criteria	Explanation
Characterizing a new RG 2-4 human pathogen or researching the properties of a RG 2-4 human pathogen or regulated toxin.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Basic characterization research incorporates creativity, novelty, and/or uncertainty of outcomes
Doing in vivo studies using a RG 2-4 human pathogen or regulated toxins. Exceptions may apply. Please contact us for information about exceptions.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Even when following approved standardized protocols, most in vivo studies incorporate creativity, novelty and/or uncertainty of outcomes Some of the uncertainties come from the unpredictability of the host’s behaviour, the potential for increased pathogenicity of the biological agent when passaged in vivo, and the potential for genetic reorganization of the pathogen while inside the host
Experimental development research where RG 2-4 human pathogens or regulated toxins are the main subject of the experiment (e.g., not only used as a control).	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Experimental development incorporates creativity, novelty and/or uncertainty of outcome If the pathogens or toxins are the central part of the experimental development process (i.e., not only used  prior to, or during the final validation steps of, the experimental protocol), this would constitute scientific research
Research activities with inactivated RG 2-4 human pathogens (no longer pathogenic) or inactivated toxins (no longer toxic) that get reactivated in the course of the experiment	Organization is subject to the HPTA Organization uses RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Research activities with reactivated RG 2-4 human pathogens or regulated toxins may incorporate creativity, novelty and/or uncertainty of outcome Reactivation or other substantial changes to the organism or toxin could increase the risk to public health
Developing new gene delivery technologies with regulated a RG 2-4 human pathogen.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Developing new gene delivery technologies incorporates the aspects of novelty, creativity, and/or uncertainty of outcome Even if a viral vector is inactivated, it may meet the definition of scientific research if there is a potential risk for its reactivation
Vaccine research and development involving a RG 2-4 human pathogen or regulated toxin, when the Food and Drugs Act does not apply (e.g., testing candidate vaccine strains, pilot scale production prior to regulatory approval). Exceptions may apply. See activities that do not meet the definition of scientific research (Part 2).	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Research and development of vaccines incorporate  novelty, creativity and/or uncertainty of outcome
Modifying, creating or producing (e.g., synthetic biology) a RG 2-4 human pathogen or regulated toxin, or making substantial changes to the properties of the pathogen or toxin.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is subject to HPTR section 3 Manipulating the properties of, modifying (e.g., genetic manipulation), creating, or producing a human pathogen or toxin inherently incorporates the aspects of creativity, novelty, and/or uncertainty of outcome
Modifying a RG 1 biological agent to generate a RG 2-4 human pathogen or an agent that produces a regulated toxin.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms to conduct scientific research	Organization is subject to HPTR section 3 Modifying a biological agent to generate a human pathogen or an agent that produces a regulated toxin inherently incorporates the aspects of creativity, novelty, and/or uncertainty of outcome

Part 2: Activities that do not meet the definition

Part 2- Activities That DO NOT Meet the Definition of Scientific Research and DO NOT Require Submission of a PAO
Activity	Criteria	Explanation
Research conducted on RG 1 biological agent or un-regulated toxins (i.e., toxins not listed on Schedule 1).	Organization is not subject to the HPTA Organization does not use a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is not subject to HPTR section 3 The requirement to submit a PAO only applies when scientific research is coupled with controlled activities using regulated human pathogens or toxins RG 1 biological agents and un-regulated toxins fall outside of the scope of the HPTA, even if research activities are being done
Research activities with an inactivated RG 2-4 human pathogen (no longer pathogenic) or inactivated toxins (no longer toxic) where there is no potential for reactivation during the course of the experiment, or non-infectious genetic material or proteins.	Organization is not subject to the HPTA Organization does not use a RG 2-4 human pathogen or Schedule 1 toxin Organization is using these microorganisms/toxins to conduct scientific research	Organization is not subject to HPTR section 3 Inactivated pathogens and other non-infectious materials fall outside of the scope of the HPTA, even if research activities are being done The requirement to submit a PAO only applies when scientific research is coupled with controlled activities using regulated human pathogens or toxins
Copying, imitating, or routine execution of standardized protocols (e.g. diagnostic procedures following ISO, CEN, CLSI guidelines). If following the standardized protocol leads to novelty and/or uncertainty of outcome, the organization is conducting Scientific Research and a PAO will be required.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is not using these microorganisms/toxins to conduct scientific research	Organization is not subject to HPTR section 3 Activities that involve following  approved standardized protocols, where the outcome is predictable AND there is no potential for novelty nor creativity, are not considered Scientific Research The requirement to submit a PAO only applies when scientific research is coupled with controlled activities using regulated human pathogens or toxins
Cultivating human pathogens to obtain genetic material while following standardized protocols, before the “scientific research” has begun. If following the standardized protocol leads to novelty and/or uncertainty of outcome, the organization is conducting Scientific Research and a PAO will be required.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is not using these microorganisms to conduct scientific research	Organization is not subject to HPTR section 3 Collecting genetic material from pathogens prior to the initiation of a research experiment following  standardized protocols would not generate novelty, creativity nor uncertainty of outcome with respect to the human pathogens or toxins The requirement to submit a PAO only applies when scientific research is coupled with controlled activities using regulated human pathogens or toxins
Using a RG 2-4 human pathogen or regulated toxins at the validation stage of an experiment, once the “research” is complete, while following  standardized protocols (e.g. validating a disinfection product or a diagnostic test, after it has been developed and optimized). If following the standardized protocol leads to novelty and/or uncertainty of outcome, the organization is conducting Scientific Research and a PAO will be required.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is not using these microorganisms/toxins to conduct scientific research	Organization is not subject to HPTR section 3 Using pathogens or toxins to validate the expected outcome of a research experiment following  approved standardized protocols would not generate novelty, creativity or uncertainty of outcome with respect to the pathogens or toxins The requirement to submit a PAO only applies when scientific research is coupled with controlled activities using regulated human pathogens or toxins.
Teaching molecular cloning techniques using a RG 2-4 human pathogen, while following standardized protocols. If following the standardized protocol, leads to novelty and/or uncertainty of outcome, the organization is conducting Scientific Research and a PAO will be required.	Organization is subject to the HPTA Organization uses a RG 2-4 human pathogen or Schedule 1 toxin Organization is not using these microorganisms to conduct scientific research	Organization is not subject to HPTR section 3 Molecular cloning activities that involve following  standardized protocols, where the process is standardized and the outcome is predictable, are not considered Scientific Research if they don’t generate creativity and/or novelty with respect to the human pathogens or toxins The requirement to submit a PAO only applies when scientific research is coupled with controlled activities using regulated human pathogens or toxins.