US FDA GRAS notifications | 'No questions’ letters for HMOs in infant formulae pave way for use in certain food applications

13 October, 2023

A ‘no questions’ letter is an acknowledgement from the United States Food & Drug Administration (US FDA), indicating that the ingredient or the product is Generally Recognized as Safe (GRAS) to eat and is permitted for use in all States. Recently, there has been a flurry of no question letters from FDA for use of Human Milk Oligosaccharides (HMOs) in infant formulae, which will allow their use in certain food applications in the US.


Upon receipt of the Notification Dossiers, and ‘no questions’ response from the FDA, the manufacturers can now use HMOs in infant formulae and conventional foods under specified conditions, if any. The ‘no question’ response is an official confirmation that these HMOs can be used.

This is of particular interest on two fronts. Firstly, the HMOs in these cases are manufactured synthetically: the Lacto-N-fucopentaose I from microbial fermentation, and 2’-fucosyllactose mixture (LNFP l/2’ FL) from a single fermentation process. This highlights that synthetic biology is gaining a strong foothold in the production of essential nutrients, supporting nutritional needs and sustainability.

Secondly, this particular HMO, manufactured by DSM-Firmenich, is launched in the US for the first time for infant formula application, as well as other food applications (conventional foods). The other recognised HMOs are hypoallergenic grade 2'fucosyllactose (2’FL) (1) and hypoallergenic grade Lacto-N-neotetraose (LNnt) for exempt infant formula(2, 3).

What are HMOs?

Human Milk Oligosaccharides are components of human breast milk, which studies have found to positively affect the gut microbiome, as well as support the digestive health and immunity for infants (4).

Securing a ‘no questions letter’

Successfully obtaining the ‘no questions letter’ from the FDA signifies the culmination of a meticulously prepared GRAS (Generally Recognized as Safe) Notice dossier. Receiving GRAS approval is a gateway for applicants to introduce their products into the US market. What’s particularly advantageous for the food & beverage industry is that these recent regulatory approvals may facilitate increased availability of HMO products in the US. It’s worth noting that GRAS notifications are not exclusive to the company that submitted the notification. Consequently, other manufacturers can use a previously accepted GRAS notification if they use the same ingredient for the same intended purpose at the established limits, if any.

Future impact

It is important for food manufacturers to monitor the evolution of GRAS applications and comprehend the significance of the GRAS Notices, since these approvals may allow other companies to innovate their pipeline of new product launches.

Support with formulation check

To learn more about how the GRAS Notice process works in the US, as well as how your product formula complies with US regulations, please get in touch at [email protected]. Leatherhead’s experienced team of scientists and regulatory experts, including former regulators and industry advocates, can support you every step of the way.

If you are a member of Leatherhead Food Research, you may use your helpline hours for support with GRAS Notices. Follow the link to learn more about Leatherhead’s product compliance services.


(1) GRAS Notices (

(2) DSM-Firmenich’s immunity and gut health-boosting HMO portfolio cleared by US FDA approval (

(3) GRAS Notice GRN 1059 Agency Response Letter (

(4) GRAS Notices (

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