- Docket Number:
- Issued by:
Guidance Issuing OfficeCenter for Veterinary MedicineOffice of Regulatory Affairs
Direct-fed microbial products are products that are purported to contain live (viable) microorganisms (bacteria and/or yeast). The labeling and promotional materials, including advertisements, for direct-fed microbial products state, suggest, or imply beneficial effects in animals associated with the products' content of viable microorganisms. (Note - This Guide does not address products marketed solely as silage additives intended to affect only silage). Direct-fed microbial products are marketed in various forms (e.g., in carriers for mixing into feed, in oral pastes, and in boluses).
The promotion and marketing of direct-fed microbial products (sometimes called probiotic products) have increased greatly the past few years. Claims for these products are unproven. Some claims may be considered puffery; others are unproven claims for significant disease conditions and for improved productivity. As competition in the marketing of these products increases, label/promotional claims have become of greater concern to FDA. Labeling and promotional material for most direct-fed microbial products bear stated or implied claims of benefits which, in theory, are derived from the products' content of viable microorganisms. Some of these products, however, are labeled or promoted only as containing live microorganisms without other claims.
The Official Publication of the Association of American Feed Control Officials (AAFCO), under Section 36 Fermentation Products, defines animal feed ingredients derived from spent fermentation processes, and under Section 96 Yeast, defines yeast products. For regulatory purposes, direct-fed microbial products are considered a subclass of fermentation or yeast products because they are similarly produced. The defined ingredients have long been used for the production of products intended for animal feed use, and FDA is unaware of safety problems associated with these ingredients. However, AAFCO's Sections 36 and 96 include a number of ingredient definitions that imply that unnamed sources of microorganisms are covered by these definitions. Some firms have marketed direct-fed microbial products derived from microoganims not listed by AAFCO or have permitted the fermentation process to proceed beyond usual maximum number of microorganisms, raising questions about the safety of these products. FDA is increasingly concerned about their safety because of the diversity of microorganisms being used and because of the manufacturing processes involved. As an example, according to some promotional material, microorganisms in direct-fed microbial products produce substances that in turn produce the claimed effects in the animal, and safety of these substances is open to question.
Because the products are often marketed in a dry form in a carrier intended to be used as a component of feed, and because of their method of manufacture and storage, there is significant question regarding whether specific products even contain the viable microorganisms they purport to contain. One way to address this problem is to require firms to guarantee a specific quantity of viable microorganisms in the labeling and then to provide a laboratory method for testing the veracity of the guarantee. AAFCO has adopted a standard statement for viable microorganism labeling. Additionally, AAFCO specifies that there should be a verifiable method to test the veracity of the microorganism-guaranteed content specified in the labeling.
The AAFCO statement is, "Contains a source of live (viable) naturally occurring microorganisms" followed by a listing of each of the microorganisms and the content guarantee, as colony-forming units per gram. The guarantee expression is specified in Regulation 4(g) of the Uniform State Feed Bill in the AAFCO Official Publication.
- A direct-fed microbial product with label/promotional claims for disease cure, mitigation, treatment, or prevention is a new animal drug and is adulterated under Section 501(a)(5) unless it is the subject of an approved new animal drug application (NADA). If the claims are in promotional material that cannot be documented as labeling, the product is misbranded under Section 502(f)(1).
- A direct-fed microbial product with label/promotional claims for affecting the structure or function of the body is a new animal drug because the claims are not derived from its food properties (i.e., the product does not act only as a source of nutrition in the animal's body) and is adulterated under Section 501(a)(5) unless it is the subject of an approved NADA. Such claims are usually improved animal productivity claims. If the claims are in promotional material that cannot be documented as labeling, the product is misbranded under Section 502(f)(1).
- Ordinarily, a direct-fed microbial product that is not labeled/promoted with any therapeutic or structure/function claims but that contains one or more microorganisms not listed in the AAFCO Official Publication is a food additive and is adulterated under Section 402(a)(2)(C), unless it is the subject of a food additive regulation.
- A direct-fed microbial product listed by the AAFCO Official Publication and labeled with the AAFCO-approved label statement for live microorganism content, and not labeled or promoted with any therapeutic or structure/function claims, will be regulated as a food as defined in Section 201(f)(3) and usually will not require FDA regulatory attention. It is anticipated that the states will monitor these products. However, if FDA has safety concerns about these products, it will treat them as not generally recognized as safe and will regulate them as food additives subject to FDA enforcement attention.
- A product containing microorganisms listed by the AAFCO Official Publication but not purported to contain live microorganisms and with no label/promotional representations other than as a source of designated nutrients will be regulated as a food as defined in Section 201(f)(3). Although claims as nutrient sources could be misleading, depending on directions for use, this type of product usually will not require FDA regulatory attention. It is anticipated that the states will monitor these products. However, if FDA has safety concern about these products, it will treat them as not generally recognized as safe and will regulate them as food additives subject to FDA enforcement attention.
REGULATORY ACTION GUIDANCE:
A direct-fed microbial product that is considered to be 1) an unapproved new animal drug, or 2) an unapproved food additive, or 3) a misbranded drug under 502(f)(1) should be considered for regulatory action. The initial action should be a *Warning* letter. Submit recommendations to Case Guidance Branch, HFV-236. Seizure or injunction should be considered if the *Warning* letter does not attain adequate correction. Consultation with Case Guidance Branch is recommended in determining the regulatory status of a product and in deciding whether seizure or injunction is the more appropriate action to recommend.
A direct-fed microbial product that appears to be misbranded under Section 403(a) will be considered for regulatory action on a case-by-case basis. Complete labels, labeling, and promotional material should be submitted to Case Guidance Branch, HFV-236, for review.
Priority for enforcement attention should be given to products that are unapproved new animal drugs or food additives, over products that are misbranded. As appropriate, the assistance of state feed control agencies should be requested in obtaining corrections of violative products.
*Material between asterisks is new or revised*
You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))
If unable to submit comments online, please mail written comments to:
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852
All written comments should be identified with this document's docket number: FDA-2021-D-0642.