RG-1 Regulatory Guidance:
Chapter 3 – Guidance on data requirements for feed approval and registration
3.9 Forage additives

Registration of Forage Additives and Mould Inhibitor Products

This section describes the regulatory status and registration requirements for forage additive and mould inhibitor products. Forage additives and mould inhibitor products are mixed feeds that do not meet exemption from registration criteria as outlined in Section 5(2) of the Feeds Regulations. As such, each forage additive and mould inhibitor must be approved and registered by the Animal Feed Division prior to its importation, manufacture or sale in Canada.

Forage additives and mould inhibitors are considered specialty products as indicated in Section 2.2 "Registration Requirements for Specialty Products", and in Table 3 of the Feeds Regulations (item # 7). They have been separated into the following types:

Type 1. Nutritive supplements applied directly to forage crops and silages, such as mixtures of molasses, urea, vitamins, minerals, flavouring agents, etc. Efficacy data is not required for Type 1 forage additives.

Product claims related to animal nutrition and/or animal production are not required for this type of product, and applications in support of product claims for nutritive forage supplements will be reviewed on a case-by-case basis. However, these products must provide a significant source of nutrients, whose guarantees must fall within Table 4 of the Feeds Regulations.

Type 2. Mould inhibitor products applied to mixed feeds (e.g., complete feeds) and approved feed ingredients, silages and hays, wherein the active ingredients are organic acids and their derivatives. Efficacy data (i.e., scientific studies) must be submitted in support of an application for registration for Type 2 mould inhibitor products.

With the exception of those related to mould growth or mould inhibition, claims are not permitted for this type of specialty product. The claim(s) must make reference to the particular forage crop(s), feedstuff(s) or type of mixed feed(s) the product has been tested on and must state the specific moisture level(s) at which the product is effective in inhibiting or reducing mould growth.

Type 3. Viable bacterial silage inoculants, including products containing registered strains of Lactobacillus buchneri, wherein the purpose of the product is the registration of primary product claims pertaining to animal production (e.g., improved milk yield) and/or animal nutrition (e.g., improved silage dry matter consumption). This type of application for registration requires the submission of efficacy data in support of product registration.

The primary claim(s) must make reference to the particular forage crop(s) the product has been tested on, as well as to the per cent dry matter content of the forage and/or silage in question. Claims relating to the chemical or physical attributes of the forage or silage (e.g., per cent heat damaged protein, ammonia nitrogen levels, NDF content in the silage) are not acceptable as primary nutritional claims for Type 3 bacterial inoculants. They are however, acceptable as secondary product claims for this type of forage additive, provided at least one primary claim (as described above) has been scientifically substantiated for the product in question.

Type 4. Viable bacterial silage inoculants wherein the principal active bacterial culture is a registered strain of Lactobacillus buchneri and whose primary purpose is to reduce or prevent yeast and/or mould growth and improve the aerobic stability of silage at feeding. This type of inoculant also requires the submission of scientific studies in support of an application for registration, wherein the registration of primary product claims pertaining to mould growth and aerobic stability are a requirement.

As with Type 3 silage inoculants, the primary product claims must refer to the specific forage crop(s) the additive has been tested on, in addition to the per cent dry matter content of the forage and/or silage in question. Secondary claims pertaining directly to animal production and/or animal nutrition are permitted, but are not mandatory for Type 4 forage additives.

Administrative Requirements

Standard registration requirements, including a completed and signed Application for Feed Registration or Renewal (CFIA/ACIA 0009) form; application fee as per Chapter 1 "Application for Feed Registration and Ingredient Approval" (Category 2); five copies of the proposed product label; a copy of the product formulation (e.g., percentage composition); an accompanying cover letter; and signing authority/Canadian agent (if applicable).

Labelling

Proposed labels for forage additives and mould inhibitors must include the complete list of ingredients and state a minimum guarantee for each one of the active ingredients in the product (Note - bacterial counts must be expressed in either colony forming units (CFU) per gram of product or CFU per kilogram of product). For Type 3 and Type 4 forage additive products bearing label guarantees for viable bacterial counts, the applicant should consult the "Guidelines for the Evaluation of Methods to Determine the Viability of Direct Fed Microbials and Forage Additives Containing Viable Microorganisms" in Section 6.2, prior to submitting the application for registration for the forage additive product in question. With regards to forage additives bearing label guarantees for enzymatic activity, the applicant should in this case refer to Section 3.6 "Regulatory status of enzyme bearing products" and Section 6.3 "Guidelines for the evaluation of methods to determine the activity of enzyme ingredients used in animal feeds" before submitting an application for registration for these types of forage additive products. Forage additive and mould inhibitor labels must reflect the standards, packaging and labelling requirements of the Feeds Act and Regulations.

Additionally, detailed directions for use must also be provided and are to reflect specific mixing instructions, different application rates, etc. Note that the directions for use, as they appear on a product label, are to be crop- or feedstuff-specific and must be substantiated by the scientific data submitted in support of the application for registration. They must also be indicative of the intended use rate of the product in question.

Also, the following label statement must appear on all forage additive and mould inhibitor product labels:

"This product may cause dermal and respiratory irritation and/or sensitivity. Appropriate protective equipment must be worn during handling."

Alternatively, if an applicant would like to have this labelling statement removed from a product label, it will be necessary to provide a scientific rationale and substantiating scientific documentation as to why the above statement is not necessary.

Requirements for Efficacy Data and Other Supporting Scientific Information

1. A cover letter explaining the purpose of the application for registration, including what type of forage crop(s), feeds, or feed ingredients the product is to be used on, the desired product claims, what type of documentation/information has been included with the application, etc.
2. The detailed product formulation and complete list of ingredients identified by generic name as listed in Schedule IV or V of the Feeds Regulations. Registration numbers for Part II ingredients (including bacterial cultures), mixed feeds, and other registered products (e.g., flavouring agents) must also be included. The registration requirements for individual bacterial cultures are described below, under the heading "Registration of Individual Microbial Strains".

   Mixed feeds, including forage additives and mould inhibitors, may not contain ingredients that are not listed in either Schedules IV or V of the Feeds Regulations. If the applicant wishes to use a currently unapproved feed ingredient as part of the product formulation in question, it is necessary to submit an application for registration to have the ingredient approved for use in livestock feeds in Canada prior to submitting the application package for the particular forage additive or mould inhibitor in question. Information concerning the application process for new feed ingredients can be found in Section 2.3 "Single Ingredient Feed Evaluation Requirements". Note that the application for registration for the forage additive or mould inhibitor cannot be reviewed unless all of the ingredients used in the product formulation are approved and listed in either Schedule IV or V of the Feeds Regulations.

3. Certificates of analysis from 3 different and recent lots of product, in addition to an accompanying analytical methodology, to substantiate the guarantee(s) that appear on the product label.
4. To support product stability and the shelf life as stated on a product label, it will be necessary to submit certificates of analysis substantiating the guaranteed shelf life (i.e., the date of manufacture and at the expiry date) for a minimum of 3 different lots of the product. The certificates of analysis for the level/concentration of the active ingredient(s) or viable microbial cells at the date of manufacture and at the expiry date must be for the same lot of product. The storage conditions used in the shelf life study should reflect the recommended storage conditions as stated on the product label.
5. A product sample(s) may be requested by the evaluation officer or Feed Laboratory to verify analytical methodologies and/or label guarantees. Samples will be requested on a case-by-case basis.
6. For new applications for registration, a minimum of 2 complete farm or production-scale studies must be presented in support of each product claim for each forage additive or mould inhibitor (i.e., Type 2, Type 3 or Type 4 products). Once a mould inhibitor or viable bacterial silage inoculant has been granted permanent registration status, a minimum of 1 complete farm or production-scale study will be required for each subsequent claim, which will be submitted as an application for significant change/re-registration. The criteria for acceptable scientific studies have been outlined below, under the heading "Criteria for scientific studies submitted in support of label claims".

Registration of individual microbial strains

With regards to the 2 types of viable bacterial silage inoculants previously described in this section (i.e., Type 3 and Type 4 forage additives), it is important to note that the bacterial cultures already assessed for use in silage inoculants are listed in Part II of Schedule IV of the Feeds Regulations. Single ingredient feeds (including bacterial cultures) located in this part of Schedule IV require registration prior to their use in livestock feeds and forage additives in Canada. Due to this registration requirement, an applicant may choose to: a) use one or more currently registered bacterial cultures, or b) in the event of an unregistered strain or culture, to submit an application to have the culture registered.

In order to register individual microbial strains, applicants should consult the "Requirement for Registration of Viable Microbial Strains" in Section 3.22, as well as the "Guidelines for the Assessment of Novel Feeds: Microbial Sources" in Section 2.7, for information concerning the documentation and information that is required to be submitted with each application for registration for an individual microbial strain.

Criteria for scientific studies submitted in support of label claims

For Type 2 mould inhibitors and Type 3 and 4 viable bacterial silage inoculants, a minimum of 2 farm or production-scale studies must be presented in support of each label claim submitted as a new application for registration. For each subsequent claim requested as part of an application for significant change/re-registration (and after the product in question has already been permanently registered), a minimum of 1 farm or production-scale scientific study is required. These investigations must meet the following criteria:

• carried out by qualified research personnel;
• performed using the target forage crop, feed ingredient and/or mixed feed for (Type 2 mould inhibitors only);
• performed using the target livestock species (in the case of Type 3 and Type 4 bacterial inoculants);
• carried out using suitable/recognized scientific methods and protocols;
• designed using an appropriate experimental design;
• designed to facilitate statistical analysis (i.e., using a suitable and recognized statistical model, proper sampling protocol and sufficient sample size);
• scientific data are analysed using appropriate statistical methods;
• consist of at least one control group and one treatment group;
• the control and experimental treatment groups must be kept in separate experimental units, so as to reduce the risk of cross-contamination (e.g., control and treated forage cannot be stored in the same silo during the ensiling (test) period);
• show a significant difference (P<0.05) between the control and treatment groups;
• indicate that the product, when used as directed, results in a significant reduction or inhibition in mould growth (Type 2 and Type 4 products) or significant improvement in one or more nutritional/animal production claims for the product (Type 3 and Type 4 products);
• where the directions for use indicate a range of inclusion rates, the testing protocol must evaluate each individual application rate;
• conducted under conditions (i.e., climate, management, crop production, feeding practices, etc.) similar to those that may be expected to occur in Canada; and
• where the results of these studies have not been published in a peer-reviewed journal, complete copies of the raw data and complete printouts of the statistical analysis are required for our review.

Description of farm- or production-scale studies

In order to clearly describe what is considered to be an acceptable farm- or production-scale study, the following criteria must be met:

• the minimum size/weight of each individual experimental unit will be from 1,500 to 2,000 kg (1.5 to 2.0 metric tonnes) for Type 2, Type 3 and Type 4 products;
• examples of acceptable experimental units include individual silos, large round or large square bales, sealed totes, etc.);
• a control group must be included in each study;
• studies must be conducted in Canada or in climates similar to those expected to occur in Canada. Studies generated from locales that differ significantly from the Canadian climate (i.e., high humidity, extreme temperatures, etc.) will not be accepted;
• data must be generated from forage crops commonly grown in Canada. Experimental results arising from studies using forages that are not typically grown on Canadian farms will not be accepted (due to the fact that claims are crop-specific); and
• for Type 2 mould inhibitors, the mixed feed(s), feed ingredient(s) or forage must be stored for a minimum period of 120 days after treatment with the mould inhibitor product.

With regards to the use of laboratory silos and other experimental-scale ensiling structures in efficacy studies presented in support of an application for registration, these smaller units may produce highly variable experimental results lacking in statistical significance and may not accurately reflect the efficacy and effectiveness of the forage additive or mould inhibitor in question when extrapolated to farm-scale or commercial conditions. Due to the potentially large variations in crop management and ensiling practices, it is felt that the use of experimental-scale ensiling structures does not accurately reflect practical conditions.

Furthermore, scientific data obtained from studies conducted in lab silos and other small-scale structures will not be accepted for new applications for registration, applications for temporary registration, or with applications for re-registration/significant change (i.e., in terms of the addition of new product claims).

The exact number of replicates required per experimental treatment and/or study will be determined by the experimental design and type of statistical analyses used in the study in question. If in doubt, a statistician should be consulted prior to beginning the scientific study in order to establish a statistically valid number of replicates.

In the event an applicant is uncertain as to whether or not their experimental design and/or testing protocol meets the criteria described above, it is recommended that the Feed Program be contacted prior to submitting an application for registration to discuss the suitability of the protocol in question.

Applications for registration for mould inhibitors (Type 2) and viable bacterial silage inoculants (Types 3 and 4) submitted without efficacy data (i.e., scientific studies), or with scientific studies that do not meet the requirements outlined above, will be not be accepted and shall be screened out and returned to the applicant.

Temporary Registrations

A temporary registration may only be granted for mould inhibitors (Type 2 products) and Type 3 and Type 4 forage additives for which all the basic registration requirements (registration of individual strains, safety, etc.) have been met, but for which the substantiating information (i.e., efficacy data) submitted in support of the application for registration did not demonstrate a statistical difference between the control and treatment group(s) (i.e., P>0.05), yet did indicate a trend toward becoming statistically significant (i.e., 0.05<P<0.10). Products bearing a temporary registration number on the label will be identified by the letter "T" in front of the registration number. Note that, as mentioned above, data submitted from laboratory silos and other experimental structures are not acceptable for temporary registration status.

The issuance of temporary registrations is considered an interim measure which allows companies to adequately comply with the conditions of their temporary registration, as outlined in their approval letter. Only one temporary registration will be granted per product and the maximum duration for a temporary registration for a forage additive or mould inhibitor will be 2 years.

1. Temporary registrations for new applications for registration
   • for new registrations given temporary registrations, no claims will be allowed on product labels, as the desired claims have not yet been substantiated by the applicant; and
   • the crop(s)/feed ingredient(s)/mixed feeds for which the mould inhibitor or forage additive has been approved for use on will appear in the product name (i.e., Silage Inoculant for Whole Plant Corn Silage or Mould Inhibitor for Complete Fish Feeds) and in the directions for use on the product label.

   With regards to new applications for registration, if the product has not been proven to be efficacious and the desired product claims have not been supported by acceptable scientific data by the end of the temporary period, and/or if other registration criteria have not been met as outlined in the approval letter granting temporary registration status to the product in question, the temporary registration will not be renewed and the product will not be considered for full registration. Hence, the current temporary registration will expire, thereby making the product in question non-compliant with Section 3 of the Feeds Act.

2. Temporary registrations granted to products that are already permanently registered
   • in the case of a forage additive or mould inhibitor that is already fully registered for use on one or more forage crops, feed ingredients, etc., and for which one or more claims are already approved, a temporary registration may be issued in the case of an application for significant change/re-registration wherein the new efficacy data submitted in support of a new product claim and/or use on a new forage crop, feedstuff, etc. only demonstrates a trend toward statistical significance;
   • in this case, the conditions of the temporary registration will only apply to the claims and the forage crop, feed ingredient, mixed feed, etc. that constitute the application for significant change;
   • a "T" will be placed in front of the existing registration number and the new crop, feed ingredient, etc., will appear in the product name and in the directions for use, but no new claims will be permitted on the product label;
   • if the conditions of the temporary registration pertaining to the new forage crop, feedstuff, mixed feed, etc. are met at the end of the temporary registration period, the product will have its full registration status restored and the new product claims (having been properly substantiated) will be added to the product label; and
   • in the event the conditions of the temporary registration are not met, no new claims will be permitted to appear on the product label and the new crops, feed ingredients, etc., will be removed from the product name and directions for use. Additionally, the label will revert back to the previously approved label (i.e., before the application for significant change was submitted) and the product will be given back its previous full registration status.

Requirements for Registration Renewal for Forage Additive and Mould Inhibitor Products

As with all registered feeds, forage additive and mould inhibitor products that have been granted permanent registration status are registered for a 3-year period, renewable by March 31 of the third year after the registration date. All applications for registration renewal must be accompanied by the following:

• a cover letter explaining the purpose of the application;
• a signed and completed application form, accompanied by the proper renewal fee;
• five copies of the product label;
• a copy of the current product formula; and
• any additional information, documentation, scientific data, etc. that is required to be submitted with application for registration renewal.

Please note that further information may be requested if safety and/or efficacy concerns emerge between the time of registration and the renewal due date.

Note that changes made to the formulation and/or to the label (e.g., claims, directions for use, crop types, etc.) of forage additive and mould inhibitor products are considered to be significant changes to these registrations. These changes cannot be submitted for review and approval at the time of registration renewal unless substantiating information and scientific data (if applicable) has been included with the application for registration renewal and are accompanied by the appropriate fees. Please consult the following section for additional information concerning the requirements for significant change/re-registration to these products.

Requirements for Amendments (Re-registration/Significant Change) to Forage Additives and Mould Inhibitors

Applications for significant change will be evaluated on a case-by-case basis. Changes including, but not limited to, the following product characteristics require the submission of efficacy data (which meets the criteria previously outlined) and/or safety data as part of the application for registration amendment:

• changes to the label guarantees for nutrients or active ingredient(s);
• changes to the product formulation that effect the efficacy and/or nutritional content of the product (e.g., addition/removal of a bacterial culture, changes to ingredients that are a main source of nutrients, etc.);
• changes to the manufacturing process that may alter the nature of the product or contribute to the introduction of chemicals (either as contaminants or additives), or changes to starting materials, processing aids, etc. used in the manufacturing process;
• changes to, or the addition of, label claims (i.e., new livestock species, addition of a different stage of production or class of livestock, addition of a new forage crop or feedstuff, etc.);
• modifications and/or additions to the directions for use and/or application rates; and
• changes to the duration of the shelf life of the product.

Please refer to Chapter 1 for additional information regarding significant changes to specialty product registrations. The application fees for these types of changes are the same as those for a new application for registration for a Category 2 mixed feed.

Formulation changes involving ingredients that are not considered to be active ingredients or a significant source of nutrients (e.g., flavours, carriers, dyes, etc.) will be evaluated on a case-by-case basis and may or may not require the submission of efficacy and/or safety data. However, it is recommended that the Feed Program be contacted ahead of time in order to determine what type of information and documentation will be required to be submitted with the proposed application for registration amendment.

Registration Requirements for Private Label Products

The private label registration process has been put in place to allow companies to commercialize a product that is already registered by another company under a different brand name. Such applications are considered standard feeds and do not require any additional safety or efficacy evaluations. Applications for registration of private labels must include a completed and signed Application for Feed Registration or Renewal (CFIA/ACIA 0009) form; application fee for a standard mixed feed (see Chapter 1); five (5) copies of the proposed product label (including the name and address of the private label registrant); an accompanying cover letter; and a letter from the company holding the original registration, signed by a person having signing authority for this company, allowing the private label applicant to use the information on file to register their product as a private label.

As the formulation of the private label product must correspond exactly to the formulation originally registered for the parent product, any mandatory information present on the original label (i.e., list of ingredients, guaranteed analysis, directions for use, caution statements, etc.), must be present on the private label. If the private labelling company also manufactures the feed, the formulation is required and certificates of analysis may be requested.

Applications for amendments to private label registrations will be evaluated on a case-by-case basis. Additional information concerning amendments to private label products can be found in Section 2.2 "Registration Requirements for Specialty Products".

Note: The registration checklist for forage additives (formerly RC-007) and the registration checklist for mould inhibitors (section 3.14, formerly RC-008) have been combined into a single Registration Checklist for Forage Additives and Mould Inhibitor Products. This new registration checklist is now located below.

Registration Checklist for Forage Additives and Mould Inhibitor Products

Administrative Registration Requirements

• Completed application package per Chapter 1

Proposed Label

• Brand name (optional)
• Product name reflecting purpose of the product and the intended use (e.g., Liquid mould inhibitor for complete livestock feeds, Silage inoculant for whole crop barley silage)
• Product claim statement(s)
• Guaranteed analysis
• Type 1 (see "Registration of Forage Additive Products" above for type definitions)
  Minimum nutrient guarantees
• Type 2, 3 and 4
  Minimum guarantees for active ingredients (e.g., active ingredient [Type 2], viable lactic acid producing bacteria (LAB) and/or enzyme activity [Types 3 and 4]). If the product contains bacterial cultures, a parenthetical listing of the genus and species of microorganisms is required in conjunction with the LAB guarantee (e.g., total viable lactic acid producing bacteria: minimum 2.2 × 10⁵ CFU/g (from Lactobacillus acidophilus and Pediococcus pentosaceus spp.))
• Complete list of ingredients by generic name as listed in Schedule IV or V of the Feeds Regulations, including registration numbers for any Part II ingredients or mixed feeds, as required
• Directions for use to permit safe and effective use of the feed
• Caution and/or warning statements (if applicable)
• Name and address of registrant
• Net weight in metric units (non-metric units of measurement may be indicated in parentheses)
• Date of Manufacture, if referred to in the expiry date (e.g., expires 12 months from the date of manufacture)
• Expiration date (shelf life in number months from the date of manufacture, or actual expiry date [e.g., June 2010], when stored under appropriate conditions)
• Registration number (to be added)

Product Composition

• Formulation / percentage composition listing amount of each ingredient by generic name as listed in Schedule IV or V of the Feeds Regulations, including registration numbers for any Part II ingredients or mixed feeds
• The registration of each microbial culture has been provided with the product formulation, as well as the registration number for any mixed feeds or Part II ingredients
• The inclusion level of each ingredient does not exceed the regulatory maximum as specified by the specific single ingredient feed definition outlined in Schedule IV or V of the Feeds Regulations

Scientific Studies

Type 1

• No scientific studies are required to support product efficacy 8

Type 2, 3 and 4

• Scientific studies are required to support the intended purpose of these products, as well as the desired product claims
• Experiments must be performed on a "farm scale" (see "Description of farm- or production-scale studies" subsection "Registration of Forage Additive Products" above for the requirements for farm-scale studies)
• Experiments must meet the criteria for acceptable scientific studies as outlined in the "Criteria for scientific studies submitted in support of label claims" subsection in "Registration of Forage Additive Products" above
• For Type 2 mould inhibitors, studies must be for a minimum duration of 120 days and scientific testing must be performed on feeds for all species which the mould inhibitor is intended

Laboratory Methods

Type 1

• No laboratory methods are required to support nutrient guarantees on labels

Type 2, 3 and 4

• Original signed Certificates of Analysis for a minimum of 3 different lots of product supporting the label guarantee(s) for the active ingredients used in the product formulation (e.g., per cent propionic acid, minimum CFU/g of lactic acid bacteria, etc.)
• Copies and information on the AOAC International or other official methodologies used to determine the level of the active ingredient(s) in the product formulation
• For type 2 mould inhibitors, the laboratory method used to count moulds must be submitted, including references for the method
• Copies and information on the analytical methodologies and relevant technical information substantiating the guarantee for an active ingredient using a novel method, as required by CFIA laboratories
• Copies and information on the analytical methodologies and relevant technical information substantiating any new or different nutrient guarantees or guarantees for new or different active ingredients, as required by CFIA laboratories
• In the event that these methods have not been peer-reviewed, additional information is required to validate the laboratory method as outlined in Section 3.6 "Regulatory status of enzyme bearing products", Section 6.2 "Guidelines for the Evaluation of Methods to Determine the Viability of Direct Fed Microbials and Forage Additives Containing Microorganisms", and Section 6.3 "Guidelines for the Evaluation of Methods to Determine the Activity of Enzyme Ingredients Used in Animal Feeds"

Expiry Date (Shelf life)

Type 1

• An expiry date and shelf life data are not required for Type 1 products

Type 2, 3 and 4

• Expiry date must appear on the label (e.g., X months from the date of manufacture, June 2010, etc.)
• Original signed Certificates of Analysis substantiating the guaranteed shelf life on the label (i.e., on the date of manufacture and at the expiry date) for a minimum of 3 different lots of product. Each Certificate of Analysis must be for the same lot of product that has been analysed at the beginning and at the end of the storage period. The storage conditions used for the shelf life study should reflect storage conditions recommended on the label.

Sample

• A product sample may be requested by the evaluating officer to validate the laboratory methodology for Type 2, 3 and 4 products (to be determined by the officer evaluating the application)

Safety Requirements

• The following statement is indicated on the label "This product may cause dermal and respiratory irritation and/or sensitivity. Appropriate protective equipment must be worn during handling"

Note: Further information may be required after a review of the preliminary submission.

• Previous
• Table of Contents
• Next