The United States Food and Drug Administration (FDA) issued warning letters to three different infant formula manufacturers on August 30, 2023. These warning letters came after several serious recalls and subsequent shortages occurred when infant formula was found to be potentially contaminated with the harmful bacteria, Cronobacter sakazakii. Many infants were sickened. Some even died.

These letters were sent to ByHeart Inc., Mead Johnson Nutrition (Reckitt), and Perrigo Wisconsin, LLC and reflected the findings they found in each of their recalls.

The FDA indicates that this announcement is not intended to advise parents and caregivers of purchasing decisions, nor is it to indicate that any product currently on the market is unsafe. These letters are intended to call out these manufacturers on what they are doing to prevent contamination events in the future, based primarily on what was discovered upon previous inspections.

At this time, the FDA does not anticipate this activity to impact availability of infant formula to the market.

This formal action requires each firm to respond within 15 working days and indicate the corrective actions they have taken and continue to take.

What is the Purpose of an FDA Warning Letter?

Warning Letters are used by the FDA to communicate violations of the Federal, Food, Drug, and Cosmetic Act, and are the agency’s primary mode of gaining prompt voluntary compliance with the Act. These Warning Letters are available to the public at the FDA website.

In this case, the letters are meant to engage the manufacturers to perform root cause investigations, cleaning and sanitation activities, and corrective actions. These responses will be used during the FDA’s next facility inspection to be sure that they are doing what they say they are doing, and what they are doing will work.

FDA Issues Statement About These Warning Letters

In a statement made by Donald Prater, acting director of the FDA’s Center for Food Safety and Applied Nutrition, he explains the reason for these recent warning letters.

“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 is committed to identifying and acting on issues early to prevent any firms from reaching the level of concern that prompted last year’s large-scale recall and contributed to the infant formula shortage.

Over the last year the FDA has continued to increase our oversight of powdered infant formula facilities. These letters are a reflection of this enhanced oversight and are intended to help the industry continuously improve the safety of their manufacturing practices, so that parents and caregivers can be confident that the formula they feed their children is safe and nutritious.”

— Donald Prater, Acting Director, FDA Center for Food Safety and Applied Nutrition

At this time, the current in-stock rates of the U.S. infant formula supply is healthy and at 85% or higher since the beginning of the year. The FDA attributes this to the hard work of people working behind the scenes in the FDA and manufacturers complying with FDA and U.S. government partners requests, outlined in the FDA’s National Strategy to Increase the Resiliency of the Infant Formula Market.

Warning Letters

Each Warning Letter was created specifically for the addressed manufacturer based on observations during their respective recalls and inspections.

ByHeart, Inc

The ByHeart, Inc letter was addressed to CEO and Co-Founder, Ron Belldegrun citing observations from inspections between December 21, 2022 and February 17, 2023.

Key points included the following:

• The ByHeart, Inc facility manufacturers an infant formula base that is used by third-party contract manufacturing facilities to blend and package as a final product. The FDA considers ByHeart, Inc responsible for any decisions and actions made on behalf of the brand.
• On October 17, 2022, ByHeart was notified of a positive Cronobacter ssp This was later confirmed as Cronobacter sakazakii. ByHeart, Inc claimed that it was a laboratory mistake, citing the laboratory was the source of the contamination result. This was successfully refuted with microbiological evidence.
• No investigation was performed to determine the cause of the contamination event and as a result, appropriate cleaning and sanitation activities were not performed at the third-party manufacturing facility. Despite FDA advice, Whole Genome Sequencing testing on environmental samples were not performed to assist in traceback investigation activities.
• Two water leak events may have contributed to the contamination event. One involved a leak in June where a skylight in the roof of the processing room allowed outside water to leak into the manufacturing environment. The other involved a leak in the sealant around the “louver” on the Drying Tower. The follow-up inspection will identify if these areas have been repaired and what is being done to ensure these issues are handled properly in the future.

Mead Johnson Nutrition (Reckitt)

The Mead Johnson Nutrition warning letter was addressed to Niall Mullane, Director of Nutrition and Commercial Quality, North American & Latin America and focused on two manufacturing facilities, the letter describes as “Zeeland Facility” inspected from February 7, 2023 through February 23, 2023 and “Wanamingo Facility” inspected from November 28, 2022 through January 9, 2023.

Key points with respect to the Zeeland Facility include the following:

• A batch of Enfamil Prosobee powder product tested positive for Cronobacter sakazakii on September 4, 2022. This product was produced from August 29, 2022 through September 1, 2022, in 3 total batches.
• The first batch tested positive and root cause analysis concluded that the third-party manufactured base powder was the source of the contamination. No other investigation of the finished product or environmental testing was performed.
• Root cause analysis did not consider the history of several internal cracks throughout the dryer system, multiple leaks at the facility, standing piles of spilled infant formula product at the facility, or other potential sources of contamination.
• A product “flush” was performed to remove the contaminated product from the system, but the firm did not follow-up to determine if the product flush was successful or sufficient to mitigate microbiological contamination from the system. The only adequate remediation of food contact surfaces contaminated by bacterial pathogens is sanitizing treatment.
• Mead Johnson Nutrition failed to provide evidence that the flush process of cleaning was sufficient or whether lapsing of sanitation processes between batches was a contributing factor in the contamination event.
• The corrective action document submitted to the FDA did not indicate sanitation or hygiene activities will be considered in future root cause investigations.
• Positive environmental swab results did not prompt the firm to conduct root cause analysis investigation.
• Water leaks indicated in internal inspection reports did not follow up with investigations.

Key points with respect to the Wanamingo Facility include the following:

• Upon receiving results of a batch of product testing positive for Cronobacter sakazakiiI, no investigation took place to determine if other products could have been impacted by the contamination event.
• Subsequent requests for corrective action submission to the FDA present inadequate explanation of root cause analysis procedures that will be used to understand what went wrong and how measures can be prevented in the future.
• Despite Cronobacter being identified in environmental samples, procedures to follow-up with an investigation outlined in the firm’s SOPs were not performed.
• Excessive amounts of powdered formula product were observed in piles on and in equipment and around the production area, in part due to improperly designed equipment (per employee statements). Follow-up photographic evidence of the area cleaned up does not show the line in use, and therefore does not indicate that the issue was resolved.

Perrigo Wisconsin, LLC

The Perrigo Wisconsin, LLC warning letter was addressed to Bart d. Shrode, the firm’s Vice President of Quality Operations in response to three separate contamination events linked back to the manufacturing facility.

Key points include the following:

• Each of the contamination events included many of the same deficiencies, primarily revolving around sanitation breaks during the production process, the use of root cause analysis tools to generate corrective actions, and the firm’s failure to conduct appropriate investigations.
• Root cause investigations all excluded conduction whole genome sequencing activities on environmental samples to verify that activities were sufficient to remediate the contamination event.
• Cleaning activities were performed prior to collecting samples, prohibiting the firm from determining if ongoing environmental contamination could have contributed to contaminated product.
• Current corrective action activities include sanitation practices, however how the firm intends to handle ongoing environmental contamination is absent in the report submitted to the FDA.

FDA Recommendations to Parents and Caregivers

The FDA recommends that parents and caregivers follow manufacturer instructions when preparing powdered infant formula. Additionally, the FDA recommends that ready-to-feed liquid infant formula should be fed to babies less than 2 months old, those who were born prematurely, and those with weakened immune systems. Liquid infant formula is made to be sterile and is the safest option.

Heating water to at least 158 °F is also recommended to help protect against Cronobacter. The water can be heated, powdered infant formula added, and then allowed to cool to body temperature prior to feeding. However, the FDA advises that certain packaging instructions for certain metabolic and specialty products may not be suitable for this procedure as it could result in loss of vitamin and nutrients.

The FDA will continue oversight and monitoring activities, conducting annual inspections of infant formula facilities to assist in prevention activities with respect to the infant formula distributed in the United States.

By: Heather Van Tassell