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WARNING LETTER

August 30, 2023

Reference #654775 and #652029

 

Dear Niall Mullane:

The United States Food and Drug Administration (“FDA”) inspected two (2) of your powdered infant formula manufacturing facilities, located in Zeeland, Michigan (“Zeeland Facility”) and Wanamingo, Minnesota (“Wanamingo Facility”). Specifically, your Zeeland Facility is located at 725 E. Main Avenue, Zeeland, Michigan 49464, and our inspection was conducted from February 7, 2023, through February 23, 2023; your Wanamingo Facility is located at 25 Main Street, Wanamingo, Minnesota 55983, and our inspection was conducted from November 28, 2022, through January 9, 2023.

During both of our inspections, FDA investigators found significant violations of Title 21, Code of Federal Regulations, Part 106 (21 C.F.R. Part 106), Infant Formula Requirements Pertaining to Current Good Manufacturing Practice, Quality Control Procedures, Quality Factors, Records and Reports, and Notifications (“the Infant Formula Rule”). At the conclusion of both inspections, FDA investigators issued a Form FDA-483, Inspectional Observations (“Form FDA-483”), listing the deviations found at each of your facilities. Based on the inspectional findings, FDA has determined that your actions have violated the Federal Food, Drug, and Cosmetic Act (“the Act”) and the Infant Formula Rule. See Sections 402(a)(4), 412(a)(3), and 301(a) of the Act [21 U.S.C. §§ 342(a)(4), 350a(a)(3), and 331(a)]. You may find the Act and FDA regulations, including 21 C.F.R. Part 106, through links on FDA’s website at www.fda.gov.1

You submitted responses to both Form FDA-483s and inspection discussion items, which included descriptions of your firm’s ongoing corrective actions. In response to the Form FDA-483 issued to your Zeeland Facility, we received responses dated March 16, 2023, March 30, 2023, and May 23, 2023. In response to the Form FDA-483 issued to your Wanamingo Facility, we received responses dated January 31, 2023 and March 31, 2023. After thoroughly reviewing your submissions, FDA is issuing you this letter to advise you of the Agency’s concerns and bring to your attention areas that still require corrective actions.

1. You 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, as required by 21 C.F.R. § 106.55(a). Specifically:

Zeeland Facility

a. On September 4, 2022, a batch of your 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 August 29, 2022 through September 1, 2022, which produced 3 batches of the Prosobee product. The Prosobee product that tested positive for C. sakazakii was produced in the first batch of this continuous campaign. Your firm’s Critical Deviation Investigation Report, which includes your root cause analysis, concluded that your third-party manufactured base powder, Prosobee Lipil Synergy, was the source of the contamination. While you identified a probable source of contamination, we note that your root cause analysis did not include further investigation of the finished product isolate or the environmental isolates recovered from the facility of your third-party supplier responsible for manufacturing your base powder.

Further investigation of these isolates, such as conducting Whole Genome Sequencing (WGS), would have provided more information about the potential role of your facility in contributing to the contamination event by indicating whether or not the strain of C. sakazakii found in finished product matched a strain of C. sakazakii previously detected at your facility. Following this inspection, we continued to have discussions with you regarding the importance of performing WGS on finished product and environmental isolates and comparing these results as part of a thorough root cause analysis via round table discussions on February 24, 2023 and May 18, 2023, as well as in FDA’s Letter to Industry on March 8, 2023. WGS results could also indicate whether or not the same strain of C. sakazakii may be contributing to multiple contamination events, which would then inform the type of corrective action and verification activities you would need to perform to sufficiently remediate the contamination from your facility following an intrusion event.

We further note that your root cause analysis did not consider other potential sources of contamination, such as a history of several internal cracks of varying lengths identified throughout your dryer system, multiple water leaks at your facility, or the standing piles of spilled infant formula product at your facility, as discussed in greater detail below. Accordingly, your root cause investigation did not consider all potential sources of contamination.

Based on your firm’s evaluation of impacted product, you destroyed the first batch of Prosobee product in the campaign run that tested positive for C. sakazakii and a portion of the subsequent batch. The remaining batches of product produced within this campaign were released, and your firm’s rationale for the release included review of your finished product testing, review of your environmental records, the findings in your root cause analysis, which concluded that a single big-bag from the third-party base blend was the source of contamination, and your performance of a product “flush,” which you stated would remove the contaminated product from the system. However, your firm did not perform genetic characterization (e.g., WGS) of the product isolate and recent environmental isolates from your facility; therefore, it is not clear how you determined that C. sakazakii and activities within your own facility could not be responsible for the contamination event. Moreover, you did not provide adequate data to demonstrate that this approach (a product flush) is sufficient to mitigate microbiological contamination from your system. The best current available science demonstrates that the only adequate remediation for food contact surfaces contaminated by a bacterial pathogen is the application of a sanitizing treatment (e.g., a thermal treatment or a chemical treatment). To date, other remediation procedures, such as physical dry-cleaning techniques, have not proven effective against eliminating pathogens from equipment surfaces.

Upon FDA’s further evaluation of your sanitation activities, the Agency learned that before and after this continuous production campaign, your firm conducted cleaning activities, which included the application of sanitizer to food contact surfaces. However, during the continuous production campaign, your firm conducted two (2) dry cleans (vacuuming) between batches that did not include the application of a sanitizing treatment to all food contact surfaces. As noted above, you did not provide adequate information or data to demonstrate that your dry clean procedures were sufficient to mitigate microbiological contamination from your system. Furthermore, you did not evaluate or consider the lack of intervening sanitation breaks as a factor in making your disposition decision regarding the impacted product within this production campaign. Therefore, upon further evaluation of your sanitation records and additional discussion with FDA, on February 19, 2023, your firm conducted a voluntary recall of the Prosobee product that was manufactured during your continuous production campaign and subsequently released into U.S. commerce.

Your corrective actions submitted in response to the Form FDA-483 provided additional information about the contamination event and your rationale behind your product release. However, your corrective action responses did not indicate that you will evaluate your sanitation and hygienic control activities in making product disposition decisions if future product testing detects a pathogen.

b. From July 1, 2022, to February 7, 2023, your firm detected C. sakazakii within your environment in high and critical hygiene zones of your facility. The goal of a well-designed environmental monitoring program is to identify environmental pathogens, such as Cronobacter spp., and any harborage sites, if present, in your facility and to implement effective corrective actions to eliminate such environmental pathogens and harborage sites. In response to finding an environmental pathogen in your facility, your Standard Operating Procedure ZSC-SC-QC MIC-SOP-03606, “(b)(4),” provides specific communication, root cause investigation, corrective action steps, and documentation requirements using your firm’s “Environmental Monitoring High & Critical Zone OOS Swab Report” (Out of Specification [OOS] Report).

FDA’s review of your firm’s OOS Reports found that three (3) Cronobacter positive environmental samples, located in “critical” hygiene zones, did not contain the information as required by your procedures. These critical swabs were collected from the (b)(4) Room on September 6, 2022, the (b)(4) Bag Room on October 4, 2022, and the (b)(4) Bed Room on October 4, 2022.

For the swab collected on September 6, 2022, in the (b)(4) Room, your root cause analysis determined that maintenance activity performed in this room on September 4, 2022, was the source of contamination. However, the employee who conducted the root cause analysis did not review any sanitation records to determine if this room was cleaned and sanitized between September 4, 2022, through September 6, 2022, prior to detecting a positive environmental sample. Because you failed to review your own sanitation records during this time frame, your root cause analysis did not consider all potential sources of contamination, which is a critical component in mitigating the presence of Cronobacter in your processing environment. Thus, it is impossible to determine whether the maintenance activity, a failure to properly conduct sanitation activities, or some other activity or event, was responsible for this positive environmental sample.

For the swab collected on October 4, 2022, from the (b)(4) Bag Room, one (1) of the vector swabs that was collected in response to the initial OOS result was out of specification for Enterobacteriaceae (EB); following this detection, you did not perform additional swabbing and testing. Your firm’s “(b)(4)” procedure states that if any of the (b)(4).” Your firm did not have any record of additional vector swab results, evidence of the minimally required EB re-swab, or completed required remediation documentation demonstrating that remediation steps were completed and verified as effective. Further, the employee completing the RCA/CAPA (Root Cause Analysis/Corrective And Preventative Action) section of the OOS Swab Report did not initial this section, making it unclear whether your firm actually performed any corrective preventative actions.

Lastly, when you discovered that the swab collected on October 4, 2022, from the (b)(4) Bed Room was positive for C. sakazakii, you did not conduct a root cause analysis for this positive finding.

FDA’s previous inspection conducted from May 23, 2022, through July 7, 2022, documented observations pertaining to deficiencies in conducting a root cause analysis in response to Cronobacter positive findings within your environment. FDA further discussed these concerns with your firm during an FDA Regulatory Meeting conducted on September 13, 2022. We acknowledge that your current corrective actions submitted in response to the Form FDA-483 describe your plans to update the “(b)(4)” procedure to describe specifications of the vector sample to include the location, zone, and results of the swabs collected as part of your root cause investigation and that you have implemented a review process for the OOS Swab Reports. We will assess the adequacy of your corrective actions during our next inspection of your facility.

c. FDA investigators observed multiple water events in your facility during the inspection. Specifically, on February 7, 2023, the following water events were observed in the (b)(4) Tower:

• In Room 57-401 (60’ elevation, high hygiene zone), a hose station located on the (b)(4) corner wall was dripping water onto the floor.
• In Room 57-206 (level 2, medium hygiene zone), the steam vent on the air handling unit for (b)(4) of the (b)(4) bed was leaking water onto the equipment below.

Additionally, on February 9, 2023, FDA investigators observed a water event in the (b)(4) Tower. In Room 901 (118’ elevation, high hygiene zone), water was dripping down the side of the heat exchanger to the floor below. Water was also on the floor approximately (b)(4) away under the heat exchanger. A water event in this heat exchanger was previously documented in your firm’s Deviation Overview Report dated November 19, 2022.

According to your firm’s Standard Operating Procedure, ZSC-SC- MFG-SOP-03429, “ZSC Water Leaks and Drain Backups: Containment/Remediation Plan,” a non-conformance (NC) report, “Deviation Overview Report” is opened for water events in high and critical hygiene zones. These reports document the immediate action, a root cause analysis, and corrective actions. During this inspection, FDA investigators reviewed your Deviation Overview Reports and we identified four (4) times where these reports did not contain information as required by your firm’s SOP. This information included a lack of documenting additional mitigation actions taken between the event and your repair and a failure to indicate whether all corrective actions were completed in response to the root cause identification.

Wet conditions – such as those areas of a manufacturing plant where water occasionally wets the area, either intentionally as part of wet cleaning, or inadvertently as the result of leaking pipes or valves or roofs – are especially favorable for the growth of Cronobacter. An ideal growth and survival environment is one which periodically gets wet even if only once every few months and then takes at least one day or more to fully dry. For example, when equipment is mounted to the floor of the plant, water may seep under the structure of the equipment and then remain wet for many days. Organisms may grow to high numbers during the time the area is wet; when the area dries, the organisms will remain viable and when Cronobacter becomes established in a “niche” environment, it may be difficult to locate the organisms. In the niche environment, the organisms grow to very high numbers during periods of nutrient and water availability. The organism may spread to other areas of the food processing plant from this niche environment by various means including employee movement, forklifts and totes, air flow, and water used during sanitation.

Your corrective actions submitted in response to the Form FDA-483 indicate that you will maintain records for all pending and completed work orders in the Deviation Overview Reports and update your SOP to include tracking and monitoring of in-progress maintenance work. We will assess the adequacy of your corrective actions during our next inspection of your facility.

Wanamingo Facility

d. On October 15, 2022, your third-party customer notified you that a finished product, non-exempt milk-based powdered infant formula tested positive for C. sakazakii. This product was blended at your facility on your (b)(4) line between September 15 – 20, 2022 and then packaged on Packaging Line #1 between September 30 – October 7, 2022.

Upon receiving notification of this result, you failed to conduct an independent root cause analysis or investigation and you did not evaluate whether other products may have been impacted by this contamination event. While you provided a document to FDA investigators during the inspection that you referred to as a “corrective action form,” this document primarily provided details surrounding the notification of the positive product, blending schedule, sanitation schedule, and environmental monitoring. This document did not provide information regarding corrective actions your firm took in response to the finished product positive. Without conducting an independent root cause analysis or investigation into the finished product positive findings, you relied on the root cause analysis conducted by your third-party customer. Per the directive of your third-party customer, you held and destroyed the lot of product that tested positive for C. sakazakii and the first pallet of the subsequent lot; however, the remaining pallets from the subsequent lot and all other lots manufactured as part of your continuous production campaign for this product were released. You did not evaluate your production and sanitation records to appropriately identify other products that were impacted by the contamination that entered your production system. Upon further evaluation of your activities with FDA, your third-party customer conducted a voluntary recall of the non-exempt milk-based powdered infant formula product that was manufactured during your production campaign and subsequently released into U.S. commerce.

Your corrective action Form FDA-483 responses included information surrounding the interaction with your third-party customer, training plans, and acknowledgment that your firm should have conducted an independent investigation into the contamination event instead of only relying on your third-party customer’s root cause analysis. However, your corrective action response lacks details on how you will conduct root cause analyses or investigations in the future and how you will evaluate your sanitation and hygienic control activities to assess any potential impact on the disposition of other products in the event that future product testing detects a pathogen.

e. From May 2022 through November 2022, you detected Cronobacter spp. within your environment, including in high hygiene locations such as the Forberg Blending area. As noted above, the goal of a well-designed environmental monitoring program is to identify environmental pathogens, such as Cronobacter spp., and any harborage sites, if present, in your facility and to implement effective corrective actions to eliminate such environmental pathogens and harborage sites. Your Environmental Monitoring SOP 024E, Cronobacter Monitoring,” dated October 30, 2017, states that when an environmental sample tests positive, there must be a follow-up and that an investigation should attempt to identify and address the potential root cause and appropriate corrective action. FDA’s review of the associated records found that you do not follow your root cause investigation procedures.

We acknowledge that your corrective action Form FDA-483 responses provided to FDA include updating your environmental monitoring program to include risk based investigational vector swabs and a detailed investigation form. Additionally, you are reviewing your Master Sanitation Schedule to identify changes in the cleaning activities and frequencies. We will assess the adequacy of your corrective actions during our next inspection of your facility.

2. You did not ensure that equipment and utensils used in the manufacture, processing, packing, or holding of an infant formula were of appropriate design and were installed to facilitate their intended function and their cleaning and maintenance, in accordance with 21 C.F.R. § 106.30.

Specifically, at your Zeeland Facility, on February 7, 2023, in the (b)(4) Can Filling Room (critical hygiene zone), your Pneumatic Scale vacuum fillers were filling Enfamil Gentlease infant formula powder. Investigators observed excessive amounts of powder in the filler housing, on the floor beneath and surrounding the fillers, and on the can conveyors prior to and after the fillers. The powder had formed into several (b)(4) piles approximately (b)(4) inches in height. Your firm staff indicated that the fillers were not adequately designed to properly fill the firm’s products, resulting in excessive amounts of spilled powder. Review of sanitation and production records indicate that an “A” clean was performed on February 7, 2023, prior to the start of this batch of Enfamil Gentlease. This “A” clean includes vacuuming powder on the front and back of fillers and also around the floors surrounding the Fillers/Seamers after cleaning. Your firm management stated that the filling areas are expected to be routinely vacuumed. Your firm’s documents “(b)(4)” and “(b)(4)” outline steps and locations for vacuuming and cleaning depending on the type of cleaning required between batches.

Your corrective actions submitted in response to the Form FDA-483 included a photograph of the cleaned (b)(4) Can Filling Room; however, it does not appear that product is being filled or that the filling line is operational at the time the photo was taken and is therefore not indicative of the equipment’s function or your hygiene practices when product is being filled and packaged. We acknowledge that you plan to hire cleaning employees with the dedicated role of vacuuming and removing powder from the environment and that you intend to replace fillers by the end of 2024. However, in the meantime, this observation remains a concern while the filling line is operational because continued excessive amounts of product spillage outside of the processing equipment can present an impediment to effective dry-cleaning practices, may provide a means for vector mechanical transfer of environmental contamination close to the line, and contribute to the development of equipment and environmental harborage sites and niches on and around the process line. We will evaluate the adequacy of your corrective actions during our next inspection of your facility.

This letter is not intended to be an all-inclusive statement of violations that may exist in connection with your products. You are responsible for ensuring that your facilities operate in compliance with the Act, the Infant Formula rule, and other applicable laws, and for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.

You should take prompt action to correct the violations noted in this letter. Failure to do so may result in legal action by the FDA without further notice, including, without limitation, seizure and injunction.

In addition to the above violations, we offer the following comment. To comply with 21 C.F.R. § 106.150, you must promptly notify FDA when infant formula product that may be adulterated leaves your establishment subject to your control as the manufacturer.

As discussed with you during each of your facility inspections, and as set forth in FDA’s March 8, 2023 letter to industry, when Cronobacter is detected in a finished infant formula product that is part of a continuous production run/campaign, all product prepared, packed, or held under the same insanitary conditions as the positive batch, whereby it may have become contaminated or rendered injurious to health, is deemed adulterated under section 402(a)(4) of the Act [21 U.S.C. § 342(a)(4)]. This would include all product produced before the contaminated lot going back to the last sanitation break unless the outcome of a root cause analysis or investigation can conclusively identify when the production system became contaminated, and that all product produced before this time was not subjected to the insanitary conditions created by the contamination event. Likewise, this would include all product produced after the contaminated lot until the next sanitation break unless some other sanitation/remediation procedure were conducted for which there is adequate information or data to demonstrate that the sanitation/remediation procedure is sufficient to mitigate the insanitary conditions created by the contamination event. As previously discussed, an adequate sanitation break requires either a full clean-in-place (CIP) cycle or the application of a sanitizing treatment (i.e., heat treatment or chemical treatment) to all food contact surfaces.

Releasing product that may be adulterated into interstate commerce without notifying FDA violates 21 C.F.R. § 106.150 and section 412(e)(1)(B) of the Act [21 U.S.C. § 350a(e)(1)(B)]. Specifically:

a. Zeeland Facility
On September 4, 2022, your Enfamil Prosobee Simply Plant-Based Infant Formula (Prosobee) powder product, tested positive for C. sakazakii. The Prosobee product was manufactured in a continuous production campaign that ran from August 29, 2022, through September 1, 2022. Upon FDA’s further evaluation of your sanitation activities and batch records surrounding this production campaign during our inspection in February 2023, FDA determined that your firm released adulterated batches of Prosobee into U.S. commerce. Ultimately, on February 19, 2023, your firm conducted a voluntary recall of these batches released within this production campaign. These batches of adulterated infant formula product left control of your facility between November 1, 2022, through January 26, 2023, and you did not notify FDA of this occurrence. (Based on recall effectiveness checks, FDA believes that your recall was effective and that you successfully removed these batches from the market.)

b. Wanamingo Facility
On October 15, 2022, your third-party customer notified you that a batch of its finished product, a non-exempt milk-based powdered infant formula that had been manufactured at your facility, tested positive for C. sakazakii. The campaign run that included this product was blended at your facility between September 15 – 20, 2022, and packaged between September 30 – October 7, 2022. Your firm relied on the recommendation of your third-party customer for the release of this product, rather than conducting your own internal investigation of the contamination event as the contract manufacturer. While you held and destroyed the batch that tested positive for C. sakazakii and the first pallet of the subsequent batch, at the direction of your third-party customer, you released the other batches manufactured in the same campaign. In conducting a root cause analysis and making product disposition decisions, your third-party customer did not evaluate your production records or consider intervening sanitation breaks as a factor. Following FDA’s review of your records and evaluation of the lack of intervening sanitation breaks, FDA determined that your firm released adulterated powdered infant formula into U.S. commerce. Accordingly, your third-party customer conducted a voluntary recall of the batches that were released from within this production campaign. These lots of adulterated infant formula product left control of your facility between October 17, 2022, through November 14, 2022, and you did not notify FDA of this occurrence. (Similarly, based on recall effectiveness checks, FDA believes that your third-party customer conducted an effective recall and successfully removed these batches from the market.)

Please notify this office within fifteen working days of receipt of this letter as to the specific steps you have taken to correct the stated violations, including an explanation of each step being taken to identify violations and make corrections to ensure that similar violations will not recur. In your response, you should include copies of related documentation and any other useful information that would assist us in evaluating your corrections. If you cannot complete corrective actions within fifteen working days, state the reason for the delay and the time within which you will do so. If you believe that your products are not in violation of the Act, include your reasoning and any supporting information for our consideration.

Please send your reply to the U.S. Food and Drug Administration, Compliance Officer Daniel Arrecis, 550 W. Jackson Blvd., Suite 800 Chicago, IL 60661 and Compliance Officer Boun Xiong, 250 Marquette Avenue, Suite 600, Minneapolis, MN 55401.

An emailed response is also acceptable. If you should have any questions regarding any issue in this letter, please contact Daniel Arrecis, Compliance Officer, at (312) 596-4263/email Daniel.Arrecis@fda.hhs.gov and Boun Xiong, at 414-326-3976/email Boun.Xiong@fda.hhs.gov.

 

Sincerely,
/S/
Ann M. Oxenham, JD
Director
Office of Compliance
Center for Food Safety and Applied Nutrition
U.S. Food and Drug Administration
/S/
Michael Dutcher, DVM
Acting Assistant Commissioner
Office of Human and Animal Food Operations
U.S. Food and Drug Administration

Cc:
Thomas J. Rud, Plant Director
Mead Johnson and Company, LLC
25 Main Street, Wanamingo, Minnesota 55983
Thomas.Rud@reckitt.com

Kirk Sakel, Interim Site Director
Mead Johnson and Company, LLC
725 East Main Avenue, Zeeland, Michigan 49464
Kirk.Sakel@reckitt.com

John C. Plummer, Supply Director North American Nutrition/Interim Site Director
Mead Johnson and Company, LLC
725 E. Main Avenue, Zeeland, Michigan 49464
John.Plummer@reckitt.com

• 1See also FD&C Act Chapter IV: Food (Mar. 28, 2018), https://www.fda.gov/regulatory-information/federal-food-drug-and-cosmetic-act-fdc-act/fdc-act-chapter-iv-food; CFR - Code of Federal Regulations Title 21 (June 7, 2023), https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=106.