FDA sends warning letters to infant formula manufacturers, unveils Cronobacter history in facilities

By Jonan Pilet on August 31, 2023

The U.S. Food and Drug Administration has escalated efforts to ensure the safety of infant formula production by issuing warning letters to three major manufacturers: ByHeart Inc., Mead Johnson Nutrition (Reckitt), and Perrigo Wisconsin, LLC.

According to the FDA, this action is occurring within the context of its ongoing commitment to enhance regulatory oversight and reflects the agency’s determination to ensure optimal conditions for producing infant formula. These letters, arising from inspections carried out over several months, cite violations of the Federal Food, Drug, and Cosmetic Act and the FDA’s Infant Formula regulations. The issuance of these warnings coincides with recalls conducted by the manufacturers in December 2022, February 2023 and March 2023 to remove potentially contaminated Cronobacter sakazakii-tainted products from the market.

Despite these actions, the FDA does not advise parents and caregivers to avoid specific infant formulas. According to the FDA, no confirmed contamination has been reported in distributed products, and the recalls have been effective in removing potentially unsafe batches from the market. Furthermore, these warning letters are not tied to ongoing recalls, and as such, they are not expected to affect the availability of infant formula.

2021-2022 Cronobacter outbreak
Between December 2021 and March 2022, the US FDA received two reports of infant deaths linked to powdered infant formula produced by Abbott Nutrition in Michigan. These reports were part of 128 complaints. While two deaths were connected to a confirmed outbreak of Cronobacter sakazakii, others were reported through the FDA’s consumer complaint system, with two mentioning Salmonella. An additional 25 incidents were categorized as life-threatening, and 80 as non-life-threatening. A variety of symptoms were reported, such as fever, vomiting, diarrhea, and blood in stool. Investigations revealed Cronobacter sakazakii in Abbott’s manufacturing environment, although genetic matches weren’t found for the strains infecting the babies. All affected infants had consumed Abbott powdered formula.

Summary of warning letters
The issuance of these letters aligns with the FDA’s customary regulatory process and aims to reinforce the significance of implementing and maintaining appropriate corrective actions in the presence of pathogens. Manufacturers are required to conduct thorough root cause investigations, subsequent cleaning and sanitation activities, and comprehensive evaluations of cleaning and sanitation practices before releasing products. Each manufacturer is allotted 15 working days to provide the FDA with an explanation of the corrective actions they are taking. The agency will review the responses and evaluate the adequacy of corrective measures during its next inspection of each facility.

ByHeart Inc.
New York, NY

An infant formula producer in New York is on notice from the FDA for significant violations of the Infant Formula Requirements Pertaining to Current Good Manufacturing Practice, Quality Control Procedures, Quality Factors, Records and Reports, and Notifications.

In an Aug. 30, 2023, warning letter, the FDA described a Dec. 21, 2022, through Feb. 17, 2023, inspection of ByHeart Inc.’s powdered infant formula facility in (redacted).

The FDA’s inspection revealed that the firm was not in compliance with regulations and resulted in the issuance of an FDA Form 483. Some of the significant violations are as follows:

1. The firm did not establish a system of process controls covering all stages of processing that was designed to ensure that infant formula does not become adulterated due to the presence of microorganisms in the formula or in the processing environment. Specifically:

a. On Oct. 17, 2022, the firm notified (redacted) that a batch of ByHeart Whole Nutrition Infant Formula finished product had tested positive for Cronobacter spp. and was later confirmed as Cronobacter sakazakii (“C. sakazakii”). The infant formula base, which was a component of the contaminated finished product, was manufactured during a continuous production campaign at the (redacted) facility from July 13, 2022, through Aug. 23, 2022. The infant formula base from this campaign was then blended and packaged as a finished product at one of their third-party contract manufacturer’s facilities from Sept. 15, 2022, through Oct. 7, 2022.

In response to the finished product positive, (redacted) conducted a root cause analysis. (Redacted) root cause analysis concluded that post-production sample handling by a third-party laboratory was the source of the contamination, essentially resulting in a laboratory error. However, the third-party laboratory provided an “OOS Result Investigational Report for Microbiological Testing” regarding the C. sakazakii findings in finished product, which concluded that “Laboratory error was not found or supported.” The third-party laboratory reached this conclusion after reviewing its internal protocols and testing conditions, finding no basis to attribute the sample results to laboratory error. Typically, a conclusion of lab error within an RCA is supported with confirmed evidence, such as written confirmation from the third-party laboratory attesting to the error. Here, there is no attestation; there is evidence to the contrary.

Despite the discrepancy between the third-party laboratory and the internal conclusion within (redacted) root cause analysis, neither the firm nor their subsidiary company, (redacted), took any additional efforts to evaluate other routes of contamination that may have contributed to this event. FDA’s review of their records obtained during the (redacted) inspection show that they did not work with their third-party contract manufacturer to further investigate the origins or root causes of the finished product positive findings.

In response to the C. sakazakii finished product findings, the firm directed their third-party contract manufacturer to hold and destroy the lot of product that tested positive for C. sakazakii and the first pallet of the subsequent lot in the same production campaign. However, they directed the release of all other ByHeart Whole Nutrition Infant Formula finished product manufactured as part of their third-party contract manufacturer’s continuous production campaign. Upon further evaluation of (redacted) sanitation and production records, and following discussions with FDA, their firm subsequently conducted a voluntary recall of the remaining five lots of ByHeart Whole Nutrition Infant Formula, Milk Based Powder with Iron from the same Sept. 15, 2022 – Oct. 7, 2022 campaign that they had previously released into U.S. commerce.

The full warning letter can be viewed here.

Reckitt/Mead Johnson Nutrition
Parsippany, NJ

An infant formula producer in New Jersey is on notice from the FDA for significant violations the Infant Formula Requirements Pertaining to Current Good Manufacturing Practice, Quality Control Procedures, Quality Factors, Records and Reports, and Notifications at two of their facilities.

In an Aug. 30, 2023, warning letter, the FDA described a Feb. 7-23, 2023, inspection of Reckitt/Mead Johnson Nutrition’s Zeeland, MI, powdered infant formula manufacturing facility and a Nov. 28, 2022, through Jan. 9, 2023 inspection of their Wanamingo, MN, facility.

Both of the FDA’s inspections revealed that the firm was not in compliance with regulations and resulted in the issuance of an FDA Form 483. Some of the significant violations are as follows:

Zeeland Facility
a. On Sept. 4, 2022, a batch of the firm’s Enfamil Prosobee Simply Plant-Based Infant Formula (Prosobee) powder product, tested positive for Cronobacter sakazakii (“C. sakazakii”). The Prosobee product that tested positive was manufactured in a continuous production campaign that ran from Aug. 29, 2022, through Sept. 1, 2022, which produced three batches of the Prosobee product. The Prosobee product that tested positive for C. sakazakii was produced in the first batch of this continuous campaign. The firm’s Critical Deviation Investigation Report, which includes their root cause analysis, concluded that their third-party manufactured base powder, Prosobee Lipil Synergy, was the source of the contamination. While they identified a probable source of contamination, the FDA noted that their root cause analysis did not include further investigation of the finished product isolate or the environmental isolates recovered from the facility of their third-party supplier responsible for manufacturing their base powder.

Wanamingo Facility
d. On Oct. 15, 2022, the firm’s third-party customer notified them that a finished product, non-exempt milk-based powdered infant formula tested positive for C. sakazakii. This product was blended at the firm’s facility on thier (redacted) line between Sept. 15 – 20, 2022, and then packaged on Packaging Line #1 between Sept. 30 – Oct. 7, 2022.

Upon receiving notification of this result, the firm failed to conduct an independent root cause analysis or investigation and they did not evaluate whether other products may have been impacted by this contamination event.

The full warning letter can be viewed here.

Perrigo Wisconsin, LLC
Eau Claire, WI

An infant formula producer in Wisconsin is on notice from the FDA for significant violations the Infant Formula Requirements Pertaining to Current Good Manufacturing Practice, Quality Control Procedures, Quality Factors, Records and Reports, and Notifications.

In an Aug. 30, 2023, warning letter, the FDA described a March 6 through April 26, 2023 inspection of Perrigo Wisconsin, LLC’s powdered infant formula manufacturing facility (Gateway facility) in Eau Claire, WI.

Based on the information the firm provided to FDA investigators during their inspection, Perrigo Company PLC (“Perrigo”) purchased the Gateway facility from Nestle on Nov. 1, 2022. The acquisition included the facility along with the U.S. and Canadian rights to the Good Start infant formula brands. Nestle remains responsible for Nestle’s current WIC contracts, with Perrigo supplying product through the Gateway facility for those contracts. Both Perrigo and Nestle indicated they will be working closely together in the transitional period following the purchase of the Gateway facility.

The FDA’s inspection revealed that the firm was not in compliance with regulations and resulted in the issuance of an FDA Form 483. Some of the significant violations are as follows:

a. The firm identified Cronobacter spp. in the following finished products:

i. During a continuous production campaign that ran from Oct. 23, 2022, to Nov. 2, 2022, two products tested positive for Cronobacter spp. The positive products were identified as Parent’s Choice Infant Formula Milk-Based Powder with Iron, which was spray dried on Oct. 26, 2022, and packaged on Oct. 27-28, 2022, and Parent’s Choice Infant Formula Milk-Based Powder with Iron, which was spray dried on Nov. 2, 2022, and packaged on Nov. 2, 2022.

Prior to the initiation of this production campaign, on Oct. 21-23, 2022, the firm conducted a major clean-in-place (CIP)/Top Down 4-Step Cleaning. On Nov. 2, 2022, when the firm received notification of the positive Cronobacter spp., they ceased production and packaging operations, placed all products on hold, and immediately initiated cleaning and sanitation activities, which entailed a major CIP/Top Down 4-Step Cleaning. FDA investigator’s review of their sanitation records indicated that there were no intervening sanitation breaks during this production campaign.

ii. During a continuous production campaign that ran from Jan. 3, 2023, through Jan. 18, 2023, a batch of their Gerber Good Start Soothe Pro powder product tested positive for Cronobacter spp. The positive product was spray dried on Jan. 11, 2023, and packaged on Jan. 12, 2023.

Prior to the initiation of this production campaign, on Dec. 31, 2022, to Jan. 2, 2023, the firm conducted a major CIP of the dryer equipment and a Top Down 4-Step Cleaning of the packaging equipment. On Jan. 18, 2023, when they received notification of the positive Cronobacter spp., they ceased production and packaging operations, placed all products on hold, and immediately initiated cleaning and sanitation activities, which entailed a major CIP/Top Down 4-Step Cleaning. FDA investigator’s review of their sanitation records indicated that there were no intervening sanitation breaks during this production campaign.

iii. During a continuous production that ran from March 26, 2023, through April 5, 2023, a batch of the firm’s Gerber Good Start Plus Iron and Calcium Fortified Milk-Based (“Gerber Good Start Plus”) powder product tested positive for Cronobacter spp. The positive product was spray dried on March 26, 2023, and packaged on March 27, 2023.

Prior to the initiation of this production campaign, on March 22, 2023, to March 26, 2023, the firm conducted a major CIP of the dryer equipment and a Top Down 4-Step Cleaning of all tote areas and the packaging room. On April 5, 2023, when they received notification of the positive Cronobacter spp., they ceased production and packaging operations, placed all products on hold, and immediately initiated cleaning and sanitation activities, which entailed a major CIP/Top Down 4-Step Cleaning. FDA investigator’s review of their sanitation records indicated that there were no intervening sanitation breaks during this production campaign.

The full warning letter can be viewed here.

Comments from the FDA
In a written statement, Donald Prater, acting director of the FDA’s Center for Food Safety and Applied Nutrition, emphasized, “Infant formula manufacturers are responsible for ensuring they make safe products, and the agency has remained in ongoing discussions with the infant formula industry to address the agency’s concerns.” The FDA aims to proactively identify and address issues before they escalate to the level of concern that triggered the significant recalls and contributed to the infant formula shortage observed last year.

The actions represent the FDA’s continuing endeavors to reinforce the safety and robustness of the infant formula supply chain in the United States. In November 2022, the FDA outlined a prevention strategy to curb Cronobacter sakazakii illnesses associated with the consumption of powdered infant formula. This approach involves collaborating with Congress to enhance regulatory tools and funding for oversight of the infant formula industry. Additionally, the FDA has partnered with the U.S. Centers for Disease Control and Prevention to support the addition of invasive Cronobacter infections among infants under one year of age to the Nationally Notifiable Conditions List. To further strengthen regulatory oversight, the FDA has begun hiring staff to establish an Office of Critical Foods and a dedicated cadre of infant formula investigators.

Recommendations for parents
For parents and caregivers, the FDA underscores the importance of adhering to manufacturer instructions when preparing powdered infant formula. The CDC recommends using ready-to-feed liquid infant formula for babies under 2 months old, those born prematurely, or those with weakened immune systems. Alternatively, extra precautions can be taken when preparing powdered formula by heating water to at least 158 degrees F or 70 degrees C to counteract pathogens, adding powdered infant formula, mixing, and then cooling the formula to body temperature before feeding.

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