The FDA has issued a general warning and a specific warning letter regarding the use of probiotics in pre-term infants. Some products have been linked with more than two dozen reported “adverse events” since 2018 and one death in 2023, the agency said.

Probiotics contain live bacteria or other microorganisms and are often used in the United States as dietary supplements. However, dietary supplements are not subject to the approval process for foods or drugs in place at the Food and Drug Administration.

The FDA reports there is “conflicting data” about safety and effectiveness of probiotics for prevention of necrotizing enterocolitis.

“Adverse events in any infant following the use of a probiotic are a concern to the FDA. We especially want to make clear that products containing live microorganisms may present serious risks to preterm infants in hospital settings,” Dr. Peter Marks, director of the FDA’s Center for Biologics evaluation and Research, said in a statement.

The FDA reported that an infant died after receiving the probiotic Evivo with MCT Oil. The product, manufactured by Infinant Health for use in hospital settings, contained the infantis subspecies of the live bacterium Bifidobacterium longum. The baby died after developing sepsis caused by the same species of bacteria.

The FDA emphasizes that it hasn’t approved any probiotic products for infants of any age, and products haven’t been evaluated for safety, effectiveness or compliance with manufacturing and testing standards.

Warning letter sent regarding Similac brand probiotic
This past week the FDA sent a warning letter to Abbott Laboratories for its Similac Probiotic Tri-Blend product, which the agency describes as an unapproved new drug and unlicensed biological product based on statements on its website and in marketing materials. The company agreed to discontinue sales of the product, the FDA said.

The warning letter states, in part, that the FDA reviewed Abbott Laboratories website and found marketing information about Similac Probiotic Tri-Blend that includes so-called clinical evidence and “The Promise of Similac Another Innovation only From Similac.”  

The product is labeled as containing, among other ingredients, Bifidobacterium infantis (Bb-02) and Streptococcus thermophilus (TH-4), otherwise known as B. infantis (Bb-02) and S. thermophilus (TH-4), and is marketed for use in preterm infants.

“based on the statements on your website and your marketing materials, your product is an unapproved new drug and unlicensed biological product that you introduced or delivered for introduction into interstate commerce in violation of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. § 331(d)] and the Public Health Service Act (PHS Act) [42 U.S.C. § 262(a)(1)],” according to the FDA’s warning letter to Abbott Laboratories.

Also, the FDA letter states that Similac Probiotic Supplement is considered adulterated because it contains Bifidobacterium infantis, which is “an unsafe food additive within the meaning of sections 201(s) and 409(a) of the FD&C Act [21 U.S.C. §§321(s) and 348]; and S. thermophilus (TH-4®), a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury, when used in preterm infants.”

The Abbott website also states, “Probiotics have shown to significantly improve outcomes” for “All-cause mortality,” “Necrotizing enterocolitis (NEC),” “Late-onset sepsis,” and “Feeding tolerance,” and that represents “Benefits of probiotics on NEC,” as “significantly reduc[ing] incidence of NEC in clinical studies.” 

Also, the website states Similac Probiotic Supplement undergoes safety testing to “ensure the probiotic is ready for hospital use.”

The FDA reviewed the Abbott website most recently this month and found that the Similac product is intended for use in the mitigation, treatment, or prevention of disease and therefore the product is a drug under section 201(g)(1)(B) of the FD&C Act [21 U.S.C. § 321(g)(1)(B)]. Additionally, according to the FDA warning letter, the product is a biological product as defined in section 351(i) of the PHS Act [42 U.S.C. § 262(i)], because it is applicable to the prevention, treatment, or cure of a disease or condition of human beings.

The FDA also said the ingredient B. infantis (Bb-02) does not meet the definition of a dietary ingredient. Under section federal law a dietary ingredient is a vitamin; a mineral; an herb or other botanical; an amino acid; a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or a concentrate, metabolite, constituent, extract, or combination of any dietary ingredient from the preceding categories. 

“B. infantis (Bb-02) does not fall within any of these categories. Therefore, the ingredient B. infantis (Bb-02) used in your product is a non-dietary ingredient added to a dietary supplement and must be used in accordance with a food additive regulation or be GRAS (generally recognized as safe) for its intended use, unless it qualifies for another exception to the food additive definition,” according to the warning letter.

The FDA says the probiotics in the Similac product are particularly dangerous to pre-term babies because their gastrointestinal systems are not fully matured, and have more permeable intestinal linings, often referred to as “leaky guts,” and motility problems, which can lead to opportunistic infections and sepsis when ingesting living microorganisms. 

“The current published literature does not show consensus among qualified experts that the use of living microorganisms in preterm infants is safe. For example, the American Academy of Pediatrics does not endorse the routine use of living microorganisms in preterm infants, finding conflicting data on its safety and efficacy in this vulnerable population, particularly those with birth weight <1000 grams,” according to the warning letter.

“Although your Similac Probiotic Supplement label states that the product is ‘not intended for infants with compromised intestinal permeability,’ and your Pediatric Product Nutrition Guide states that your product is ‘not intended for infants with intestinal permeability,’ other marketing materials of yours directly contradict these statements. 

“For example, your infographic titled, ‘How Probiotics Can Help My Preterm Infant, Infancy is an important Time in Developing a Healthy Gut Microbiome,’ acknowledges that the gut is not fully developed in many preterm infants and nonetheless recommends your product be administered to this population because probiotics ‘increase the number of good bacteria in the gut, promoting a healthy microbiome.’

“Moreover, you categorize your product as a dietary supplement for premature/low-birth-weight infants in your Pediatric Product Nutrition Guide, and in your ‘Probiotics and Preterm Infants: Clinical Evidence’ marketing handout that your sales representatives distribute to NICU dieticians, you have indicated that this product is designed specifically for preterm infants.

“Furthermore, statements on the product page of your website indicate your product is available for ‘Hospitals and institutions’ and your ‘The Promise of Similac: Another Innovation only From Similac’ information sheet describes product testing to ensure it is ‘ready for hospital use.’ The care of infants in a healthcare setting includes care of preterm infants; therefore, this use is further evidence of the intended use of this product for consumption by preterm infants.”

In its warning to Abbott Laboratories the FDA advises company officials to comprehensively review their website, product labels, and other labeling and marketing materials to ensure that you are lawfully marketing your product in full compliance with federal law. Failure to adequately address this matter could result in the FDA taking enforcement action without further notice, including, without limitation, seizure and/or injunction.