Appendix E-2: Viable microbial products (VMPs)

1. Introduction

1.1 Background

Currently, many viable microbial products (VMPs) fall under the veterinary drug category primarily due to their claims and/or modes of action. Health Canada’s Veterinary Drug Directorate (VDD) and the Canadian Food Inspection Agency’s (CFIA) Animal Feed Division are providing different pathways for their registration by increasing the flexibility for classification. The classification criteria for VMPs have been reconsidered, recognizing that the mode of action of these products may involve modification to the gut microflora and the gut environment without necessarily classifying them as veterinary drugs. VMPs classified as feeds may fall under a new category: "Gut modifier (gastro-intestinal modifier)" which may be indicated on the label. Products under the Gut modifier category would also carry a nutritional or production/performance claim consistent with products regulated under the Feeds Act and Regulations examples of which can be found in Table E-2.1.

1.2 Purpose and Scope

The purpose of this appendix is to provide guidance and clarification concerning the revised regulatory classification of products containing viable microorganisms intended for livestock species.  VMPs are fed to livestock as a source of viable cells whose main purpose in the diet is to have beneficial effects in target livestock species.

Please note that non-viable organisms and their products, as well as forage inoculants, are excluded from the scope of this specific appendix; refer back to the main document for appropriate classification considerations.

2. Definitions:

Viable microbial products are products that contain live microorganisms (bacteria, yeast, fungi, algae and/or protozoa). These products refer to a live micro-organism biomass or single specified strain. They can include individual or multiple microbial strains and be incorporated (in a diluted form) into products such as mixed feeds, boluses and other dosage forms.

3. Relevant classification criteria:

As with any product classification, the criteria outlined in the guidance document should be consulted. The following additional criteria will be considered in the classification of VMPs for use in livestock species. 

3.1 Properties of Microbial Strains

Knowledge of the properties of microbial strains or strain combinations may be incorporated into the classification decision of a product. Strains with known antimicrobial properties such as: bacteriocin production, antimicrobial peptide production and/or bacteriophages, may be considered drugs.

3.2   Intended Purpose and Indications (Claims)

An indication (or claim) needs to be provided for all viable microbial products. These claims should be based on a measurable outcome and supported by valid scientific evidence. The proposed claim is a key consideration for classification, as follows:

• Therapeutic claims may include the prevention or treatment of a disease condition or state, the mitigation of clinical signs, or disease risk reduction. Products with therapeutic claims are considered drugs and may consist of viable microbial products that claim to target a particular pathogen(s) inside the gastro-intestinal tract, to reduce pathogen load, or to prevent and/or treat a particular disease condition.
• Nutritional or Production/Performance claims refer to the provision of nutrients, directly or through their improved availability, and their digestion or absorption.  Products having claims that include the support of the maintenance, growth, and improved performance of animals may be associated with livestock feeds.
• General health claims are expected benefits in maintaining or promoting the health and welfare of animals. General health claims may be acceptable for the notification of Veterinary Health Products^{Footnote 1} (VHP).

Statements that refer to "replacement for antimicrobials" are not acceptable for any products.  Product claims need to stand alone and should not reference another product or product type. Examples are provided in Table E-2.1 below.

Table E-2.1:  Examples of potential indications/claims separated based on the governing regulations and regulatory approval processes.

Food and Drugs Act; Food and Drug Regulations		Feeds Act; Feed Regulations
Therapeutic Claims – New Drug (Drug Identification Number)	General Health Claims – VHP (Notification Number)	Feed Claims – Feed (Registration Number)
Treatment/Prevention of Disease: For the control of salmonellosis Increases resistance to E. coli infections For the prevention and/or treatment of diarrhea caused by E. coli Reduction in the incidence of necrotic enteritis As an aid in the reduction of digestive disturbances Pathogen reduction: Reduces clinical cases of diarrhea by preventing the adhesion of E. coli  in the gut Limiting the spread of disease through the reduction in the shedding of Salmonella spp.	Promotes a healthy gut flora For good intestinal health Maintains balance of healthy microflora Provides friendly bacteria that play an important role in basic digestion, proper metabolism and overall well-being Supports the function of the immune system Promotes healthy intestinal microbiota To help maintain normal, healthy intestinal micro-flora and normalize bowel ecology Helps to support a healthy digestive system by encouraging stomach micro-flora Maintains normal stool quality Plays a role in the maintenance of normal bowel mucosa and supports the evolution of healthy intestinal microflora.	Replenishes (or maintains) intestinal flora after a physiological event As an aid in odor control Digestion: Improves the digestibility of nutrients Increases surface area/length of intestinal microvilli for nutrient absorption Improves rumen development (calves) Stabilizes rumen pH Production and Performance: Improves feed intake/Improves palatability Improves feed efficiency/conversion Improves daily weight gain Improves milk production/yield Improves weaning weight Improves carcass  quality and carcass  yield Improves production and egg quality rate/ total eggs laid per season As an aid in maintaining weight gains and stimulating appetite during periods of stress caused by moving, vaccination, temperature changes and castration

Note: This table is for illustrative purposes only and should not be considered as an exhaustive and complete list.  If a product's claim or indication is not listed in the above, please contact VDD (as a single-window access for classification) for further assessment.

3.3 Dosage Forms:

Consistent with the Guidance document, dosage forms that require forcible administration (eg. boluses and tablets) are regulated under the Food and Drug Regulations. Oral dosage forms that do not require forcible administration may be regulated under either the Food and Drug Regulations or the Feed Regulations depending on other classification criteria. To ensure consistent regulatory oversight and application of standards in safety, efficacy and quality, products in oral dosage form will be regulated as illustrated in Table E-2.2.

Table E-2.2:  Potential regulatory pathways of VMPs in oral dosage forms separated based on the governing regulations and regulatory approval processes.

Mode of Oral Administration	Food and Drugs Act; Food and Drug Regulations		Feeds Act; Feed Regulations
	Therapeutic Claims – New Drug (Drug Identification Number)	General Health Claims – VHP (Notification Number)	Feed Claims – Feed (Registration Number)
Forcible Administration (e.g., bolus, tablet, drench)	Yes	Yes	No
Mixed in Feed	Yes	No	Yes
Top-Dressed on Feed	Yes	No	Yes
In-Water	Yes	No	Yes

For further information on VHPs and the VHP notification pathway:

• Veterinary Health Products
• Veterinary Health Products – Notification Program

4. Other Considerations:

As indicated in the Guidance document, the mode of action criterion is not always definitive and may not necessarily be used for the classification of viable microbial products. The rationale behind this approach is that the different mode(s) of action of these products are complex, not well understood, can occur in combination and vary depending on the intestinal environment. Therefore, references to mode(s) of action related to intestinal flora will no longer automatically trigger a drug classification on its own. This decision supersedes the previous classification approach elaborated by VDD and the Animal Feeds Division (AFD) in a 1997 Memorandum of Understanding. 

• It is possible that for certain viable microbial products, additional criteria may need to be considered for classification (e.g., strength (concentration), dosage and conditions of use etc.)
• When proposing a claim for classification careful thought should be given to the potential supporting evidence available and the product's intended use within a complete health management program implemented under the supervision of a veterinarian and/or animal nutritionist.