T-4-103 - Guidelines for Research Authorizations for Testing of Novel Supplements

May 2013

1. Introduction

1.1 Purpose

Research Authorizations exempt supplement products used for experimental purposes from registration under the Fertilizers Act and Regulations. This document is designed to instruct applicants wishing to conduct research trials on novel supplements, about the requirements for obtaining a Research Authorization.

1.2 Regulation of supplements in Canada

Most supplements, other than those listed in section 3.1 and Schedule II of the Fertilizers Regulations must be registered prior to importation or sale in Canada. In order to obtain registration, applicants must demonstrate that the product is safe with respect to human, animal, plant health and the environment, efficacious for the intended purpose and properly labelled to avoid misrepresentation in the marketplace. When information necessary to support product registration is not available, applicants may wish to conduct the scientific research to gather the data. For more information on registration of supplements please refer to Trade Memorandum T-4-107 Registration of Supplements under the Fertilizers Act.

1.3 Types of supplement products

Research authorizations must be obtained prior to environmental release of all novel supplements, that is, supplements that are not registered and not exempt from registration or that contain a novel trait. Examples of such products include wetting agents, live microorganisms, plant growth regulators, signalling compounds, humates, etc.

2. Definitions

biotechnology: means the application of science and engineering to the direct or indirect use of living organisms or parts or products of living organisms in their natural or modified forms

environment: means the components of the Earth and includes (a) air, land and water, (b) all layers of the atmosphere, (c) all organic and inorganic matter and living organisms, and (d) the interacting natural systems that include components referred to in paragraphs (a) to (c)

fertilizer: means any substance or mixture of substances, containing nitrogen, phosphorus, potassium or other plant food manufactured, sold or represented for use as a plant nutrient

novel supplement: means (a) a supplement that is not registered and not exempt from registration, or (b) a supplement that is derived through biotechnology and has a novel trait

novel trait: in respect of a supplement derived through biotechnology, means a characteristic of the supplement that (a) has been intentionally selected, created or introduced into a distinct, stable population of the same species through a specific genetic change, and (b) based on valid scientific rationale, is not substantially equivalent, in terms of its specific use and safety both for the environment and for human health, to any characteristic of a similar supplement that is in use as a supplement in Canada and is considered safe for use as a supplement in Canada

release: means any discharge or emission of a supplement into the environment or exposure of a supplement to the environment

supplement: any substance or mixture of substances, other than a fertilizer, that is manufactured, sold or represented for use in the improvement of the physical condition of soils or to aid plant growth or crop yields

3. Exemptions from Research Authorizations

3.1 Product

Several types of products regulated under the Fertilizers Act and Regulations are exempt from the Research Authorization requirement. Applicants wishing to conduct research trials on the following types of products in Canada may do so without obtaining authorization from the Fertilizer Safety Office (FSO), CFIA:

(a) Products OTHER than supplements that are subject to regulation and/or registration under the Fertilizers Act. This includes nitrogen, phosphorous and potassium fertilizers, micronutrient fertilizers, fertilizer pesticides etc.

(b) Supplement products exempt from registration under the Fertilizers Act (listed in section 3.1 and Schedule II of the Regulations. This includes products such as composts.

(c) Supplements that are currently registered. Please note that registered supplements are exempt from the Research Authorization requirement ONLY if tested according to the directions for use prescribed on the approved product label.

3.2 Contained research trials

The trigger for regulating research trials is environmental release. The FSO does not consider supplements tested in contained facilities to be released. This research may be conducted without a Research Authorization from the FSO of the CFIA. If there are any questions about how your facility would be classified, please contact the FSO.

Research carried out in greenhouses may or may not be considered contained. To qualify as a contained trial, the greenhouse must be adequately contained to prevent the release and spread of the supplement into the environment. Hence, applicants wishing to exempted from the Authorization requirement must submit a detailed description of the greenhouse where the trials are to take place and the procedures used while handling the supplement.

The information should include: qualifications and training of the personnel, air handling systems, water and effluent handling systems, description of the treatment areas, isolation features and containment procedures. The confinement conditions of each facility are reviewed by the FSO on a case by case basis and, if deemed appropriate, the exemption is granted.

4. Guidelines for research trials

4.1 General criteria

All research trials conducted on novel supplements in Canada must meet the following general criteria:

(a) Research trials must be conducted by a qualified researcher using scientific and statistically valid methods.

The researcher(s) responsible for the field trials must have successfully completed a Bachelor's or higher degree in agriculture or a related scientific field, or have previous experience in carrying out scientifically sound research trials on agricultural product performance.

(b) Good laboratory practices and appropriate quality control procedures must be followed. The company or research institute does not necessarily need to be GLP certified.

(c) The research institution must ensure the safety of its employees throughout the duration of the trial.

(d) The research must be conducted in areas where spread of the supplement being tested outside the test site is not likely to occur (example: via run-off, erosion, drift, leaching etc. and bystander exposure to the supplement or to treated plants or soil is limited.

(e) Treated plants, growing media and unused product must not be sold or distributed and all supplement and plant material, including harvested crops, from the treated sites must be safely disposed of at the completion of the testing*. Applicants are required to propose a method of safe disposal which may vary based on the nature of the supplement (microbial vs. chemical), the probability of its spread and establishment in the environment, and the relative risk associated with the release. For further guidance on safe crop disposal methods please contact the FSO, CFIA.

4.2 Post-harvest monitoring

Release of some novel supplements for scientific research may require that the experimental site be monitored after termination of the trial. In such cases, the sampling protocols and the analytical methods used to detect and monitor the persistence of the supplement in the environment must be approved by the FSO prior to trial establishment. Once approved, the monitoring plan and procedures shall be included in the Research Authorization as one of the conditions of the release.

If at any point in time during or after completion of the research project, it is determined that the release of the supplement has any adverse effects on plant, animal, and human health or the environment, appropriate measures such as fumigation of the soil and/or post harvest land restrictions will be implemented at the cost of the applicant and/or responsible researcher.

4.3 Experimental Design

It is strongly recommended that applicants request a review of the experimental design and follow the recommendations made by the FSO.

4.4 Documentation required for all trials

All applicants wishing to conduct research trials on novel supplements must submit the following documentation to the FSO of the CFIA:

a) Application form

All applicants are required to complete the Application for Research Authorization; form (Appendix A). This form must be filled out in its entirety and signed by the applicant and/or the researcher.

(b) Experimental-use label

An experimental-use label or information sheet(s) is required to accompany the test product and must be included together with the application form. The purpose of the experimental-use label or information sheet is to ensure that applicators of the product are provided with the appropriate use, handling and disposal instructions. These labels or sheets must also be provided to the researcher in charge, and made available to all workers who will be directly involved in the trial. Once approved by the Fertilizer Safety Office, the experimental-use label or information sheets must be affixed to the supplement container(s) to be used during the trial. The information should be legibly typed in either official language and should correspond to the directions for use in the intended research project.

The following information is required to appear on the experimental-use label or information sheet accompanying the product. The items indicated below with an asterisk (*) must always be included.

• *"READ LABEL BEFORE USING" statement
• *"FOR EXPERIMENTAL USE ONLY" statement
• *"Not for sale. "Not for distribution to any person other than a researcher or cooperator" statement
• *Name, product identifier
• *Name and address of the manufacturer
• *Net contents
• *Active ingredient and concentration
• *Directions for use including crop species, method of application and application rate
• Storage requirements, expiry date (if applicable)
• *Product disposal and (if applicable) sterilization methods (the label should indicate that "any unused product should be returned to the manufacturer unless appropriate sterilization methods are available")
• *Crop disposal method (must correspond to the method prescribed in the Research Authorization)
• Hazard warnings and precautions (if applicable)
• First aid information (if applicable)
• Personal protective equipment during transport, mixing, loading, application, disposal and spill cleanup (if applicable)
• Method of equipment cleaning or sterilization
• *Name and contact information for the researcher in charge and cooperator

(c) Trial Maps

It is the responsibility of each applicant to provide the geographical location of the trial site including legal land description and detailed maps. General test locations may be provided with the application forms, but the exact maps must be submitted no later than 21 days after trial establishment. Maps of all field trials must be legible and precise to allow CFIA inspectors to locate the trial site, this year and in subsequent years if the need should arise. Maps should be on a blank page with crisp line drawings and block letters. Maps on lined or graph paper, or photocopies of road or topographical maps will not be accepted. The following information must be clearly printed on each map:

(a) The location of the trial site (city, town, province). For trial sites established within town/city limits, include the physical street address. For trial sites established outside town/city limits, include the distances and directions from the nearest town/city, as well as legal land description.

(b) Compass directions, with North at the top of the page.

(c) The legal land location.

(d) Measurements between the trial site and permanent surrounding landmarks, in other words, the exact trial location coordinates. Permanent markers should be placed to identify the trial boundaries. When this is not possible, a minimum of 3 separate measurements from two permanent nearby landmarks to two of the site corners (to the nearest ½ m) must be provided for precise location of the site.

Global Positioning System (GPS) coordinates can also be used to mark the outer limits of the test area (example; for a rectangular plot, at the four corners) and three permanent surrounding landmarks. The permanent markers (landmarks) must be found within a 10km radius of the field site. If using a building or other large object as your permanent marker, please be specific as to which part of the building was used as a reference (example; south-west corner of the red barn). In addition, please choose well spaced landmarks (do not take 3 reference measurements from the same building). Please note, that maps are still required even if trial locations are identified using GPS coordinates (the GPS coordinates should be marked on the map).

(e) Exact trial dimensions and a description of surrounding crops.

(f) The name and phone number of the field contact.

(g) The Submission Control Number designated by the FSO of CFIA (required on the final map only).

(h) The date of the trial establishment.

An example of an acceptable map (with and without GPS coordinates) is provided in Appendix B of this document.

5. Categories of Research Authorizations

5.1 Category A

Category A is a streamlined regulatory process which targets testing of supplement products that pose negligible risk to plant, animal, human health and the environment (example; non-Genetically Modified (GM) rhizobia). Once the trial has been assigned to Category A (based on the information provided on the application form) and the appropriate fees have been received by the FSO, applicants will receive a generic Research Authorization that outlines the conditions of the trial. The conditions prescribed in the Authorization must be adhered to throughout the duration of the trial.

5.2 Category B

Category B applies to novel supplements that have not been previously assessed by the Fertilizer Safety Office, are genetically modified, or in some way represent a potential risk to human health or the environment. If deemed necessary the CFIA may impose specific conditions to mitigate the risk, or refuse to authorize the trial.

Once the information outlined below is reviewed and the appropriate fees have been received by the FSO, applicants will receive a Research Authorization which describes the specific conditions of the trial. The conditions prescribed in the Authorization must be adhered to throughout the duration of the trial. The draft authorization will be provided to the applicant for comment prior to the final approval.

5.2.1 Additional Information for Category B

In addition to the application form and the experimental-use labels, the following information must be submitted for Category B authorizations:

(a) Manufacturing process and quality control procedures.

A brief description of the manufacturing process together with the quality control procedures implemented to ensure purity of the final product and consistency in production is required. If the information is not available to the applicant, it may be provided directly by the manufacturer of the product. In such cases all confidential business information shall not be disclosed to any person or party including the applicant without written authorization of the manufacturer.

(b) Safety rationale

A brief safety rationale, based on experimental data and/or published scientific literature must be provided for the product and all its ingredients. In this rationale please identify any potential risks the supplement may pose towards human health and the environment and discuss all studies where adverse effects associated with the use of the active ingredients were reported. If the trials are conducted on genetically modified organisms, please provide information on the method of modification, and a detailed description on how the organism differs from the parent organism. Peer reviewed literature must be referenced in the safety rationale

(c) A monitoring plan and procedure

A monitoring plan of the spread and establishment of the supplement in the environment throughout the duration of the trial must be provided. The methodology used to identify and trace the novel chemical or microorganism must be approved by the FSO prior to implementation.

(d) Confinement procedures

A detailed description of the confinement procedures intended to mitigate the establishment and spread of the supplement in the environment must be submitted for research trials conducted both in a greenhouse and in the field. These include but are not limited to descriptions of the packaging of the supplement during shipment and storage, timing and application methods, implementation of buffer zones (if required), research area entry restrictions, equipment cleanup and sterilization, etc. If deemed necessary the CFIA may impose additional confinement conditions on the trials to mitigate the spread of the supplement.

(e) Contingency plan

All applicants must provide a contingency plan designed to mitigate any adverse effect(s) of an accidental release of the supplement. This includes a detailed description of cleanup and disposal procedures in cases of accidental spill or release of the product, treated plant material or growing medium contaminated with the supplement.

5.3 Category C

Category C is reserved for renewals of past exemptions. Renewals include monitoring of a test site without re-application of the supplement and subsequent years of testing of the same supplement on the same crop group. Additional sites may be added upon applicant's request. A new Category C authorization is required for each additional calendar year in which testing takes place, and can be obtained by filling in the same application form as for Categories A and B. For Category C, a signed statement indicating that all parameters of the trial are the same as in the previously granted Authorization is required. The responsible researcher or the applicant must sign the declaration. Once the information and the appropriate fees are received by the FSO, the applicant will receive a Research Authorization containing the same conditions as those set out in the previous year (unless new information has come to light to merit changes).

6. Administrative requirements and submission review procedures

6.1 Submission deadlines

All application packages must be submitted at least 90 days prior to the trial start date.

6.2 Submission review procedures

All applicants requesting a Research Authorization are required to fill out a generic application form (Appendix A) that provides basic information about the supplement under test and the trial. Based on this information, the FSO assigns an appropriate research category, identified additional information (if any) required, and requests the appropriate fees. The three categories of Research Authorization are described in section 5.

The review of the Applications for Research Authorization will be completed within 30 days of their receipt. Once the application form has been reviewed, the FSO will assign a Research Authorization Category to the trial, inform the applicant (in writing) of the decision and request any additional information (if applicable) and the appropriate fees. The applicants will then have 30 days to submit the information and the fees. Once the fees are received and the information provided satisfies the requirements of the Regulations, a Research Authorization will be granted. Please note that the research trials cannot commence before receiving the Research Authorization and the trials must be conducted in accordance with the conditions prescribed therein.

6.3 Number of applications

For all categories of Authorizations, an application form must be submitted for every year of testing for each product and crop species or crop group. Provided that the product, trial method and crop species or crop group are the same, trials conducted at multiple sites may be reported under the same Research Authorization. If applicants wish to report multiple trials conducted on crops from the same crop group under one application, a scientifically valid rationale demonstrating crop similarity must be submitted to and approved by the FSO. This rationale should include taxonomic or otherwise physiologically relevant evidence indicating that the crop species within the group will respond to the supplement under test in the same/similar manner. Please note that obtaining a research authorization for a crop group does not automatically guarantee that the supplement will be granted registration for that crop group. Efficacy data may be required for each crop species individually.

6.4 Fees

(a) Category A - Research program review without safety $250.00 + HST

This type of review of a research exemption involves only the research protocol review and no evaluation of safety data. A safety assessment for each novel supplement is conducted only once.

(b) Category B - Research program review with safety $500.00 + HST

This type of review includes safety assessment of the novel supplement. Note that the safety assessment is not a full safety assessment for product registration. Additional information may be required at the time of product registration, or for a crop destruct waiver for certain products.

(c) Category C - Research program renewal $100.00 + HST

6.5 Amendments

Amendments to the application or the final Research Authorization must be submitted to the Fertilizer Safety Office for approval prior to implementation. This includes minor amendments to the application, such as adding or removing trial sites or changes in the total trial area.

7. Importation for research purposes

Applicants wishing to import novel supplements into Canada for experimental purposes must first apply for a Research Authorization. Only if the research trials are authorized may the supplement be imported and the quantity shall not exceed the total amount of product required to conduct the testing. In some cases applicants may also be required to obtain an Import Permit from the Animal and/or Plant Health Import/Export Office, CFIA.

8. Sale and advertising of supplements used in research trials

Unregistered supplements that have been exempt from registration for scientific purposes cannot be sold, distributed or offered for sale in Canada.

9. Inspection

All research trials on novel supplements conducted in Canada may be subject to inspection by the CFIA inspectors. The Fertilizer Safety Office will generate a detailed inspection report form designed to verify compliance of the trial with all conditions prescribed by the Authorization. The CFIA inspectors may require assistance from the researcher/cooperator of the trial to fill out all the required information on the report form. Cooperation of the researchers is greatly appreciated. Following the field inspection, the inspector will send a completed report form to the FSO for review and follow up. Any changes to the research protocol must be submitted to and approved by the FSO prior to trial inspection.

10. Records and data reporting

In addition to monitoring via data collection, the trials must be monitored by the responsible researcher on a regular basis (minimum frequency of once every four weeks). Observations should be recorded on a plot observation sheet. The FSO does not provide templates for these observation sheets. However, the type of information recorded should include any observation(s) that may aid the applicant in the interpretation of efficacy data collected from the experimental plots (e.g. weather conditions such as drought, excessive precipitation, extreme temperatures; insect infestation, incidence of disease, weediness etc.).

11. Contact

Canadian Food Inspection Agency
Plant Health and Biosecurity Directorate
Crop Inputs Division
Fertilizer Section
59 Camelot Drive
Ottawa, Ontario
K1A 0Y9
Canada
Telephone: 613-773-7189
Facsimile: 613-773-7163

Appendix A

Application Form for Research Authorization

APPLICATION FOR RESEARCH AUTHORIZATION
Under the Fertilizers Act and Regulations

This document acts as written notification of the proposed release of the novel supplement to the Minister of Agriculture and Agri-Food. The information provided in this document is required by the Canadian Food Inspection Agency for the purpose of evaluating the proposed release of the novel supplement. Some information may be accessible or protected as require under the provisions of the Access to Information Act. Information that could cause you or your organization injury if released is protected from disclosure as defined in section 20 of the Access to Information Act.

Please download the Application Form for Research Authorization.

NOTE: Application must be received 90 DAYS PRIOR TO TRIAL ESTABLISHMENT. One application is required per product per crop/crop group. TYPE OR PRINT CLEARLY. LEAVE SHADED AREAS BLANK.

i. The product will be tested in areas where movement out of the test site is not likely to occur (example; via run-off, erosion, leaching, etc.) and bystander exposure to the product or to treated plants or soil will be limited;

ii. I will be responsible for, and assume the costs of, the safe disposal of the novel supplement and all crops produced on the land or growing medium to which the novel supplement is applied;

iii. Treated plants, growing media and unused product will not be sold or distributed and crop harvested from the treated plots will be safely disposed of at the termination of the testing; UNLESS a waiver from the crop destruct requirements has been granted by the Fertilizer Safety Office (please attach a copy of the waiver)

iv. I will notify the researchers and/or the research employees involved in the project regarding the conditions of the authorization and provide them with the experimental-use label or information sheet.

v. I will immediately notify the CFIA if any new information regarding risks to the environment or to human health associated with the release of the novel supplement come to light.

vi. I will provide official maps of all trial sites to the CFIA no later than 14 days following the commencement of the trial

vii. I will immediately report any unanticipated effect attributable to the release of the novel supplement.

January 29, 2007

Appendix B

Examples of Acceptable Maps