FDA Warning Letter Highlights the Requirement for Reporting Non-compliant Product to Reportable Food Registry

In December of 2022, a feed facility of Nutra Blend, LLC subsidiary of Land O’Lakes., mistakenly added drug ingredient into a non-medicated feed which resulted in deaths of multiple calves. While FDA cited the company for issues with its Preventive Controls Plan, FDA also hit on the company for failing to report the non-compliant product into the Reportable Food Registry.  And this is an important regulation that may not be well known or can be overlooked.

What is the Reportable Food Registry?

• "The Reportable Food Registry (RFR or the Registry) is an electronic portal for Industry to report when there is reasonable probability that an article of food will cause serious adverse health consequences. The Registry helps the FDA better protect the public health by tracking patterns and targeting inspections." 
• Registered Food Facilities that manufacture, process, pack, or hold food for human or animal consumption ...are required to report when there is a reasonable probability that the use of, or exposure to, an article of food will cause serious adverse health consequences or death to humans or animals.
• Must provide amended reports as necessary- for example, FDA understands that it may take more than 24 hours to perform investigation activities and obtain information such as the results of any investigation of the root cause of the adulteration (when applicable) and the disposition of the reportable food.
• Portal - https://www.safetyreporting.hhs.gov/SRP2/en/Home.aspx?sid=938fc413-86cd-4670-8fe4-64e25d253c33

In this case, the company knew there was an issue, but fumbled around trying to determine how bad the issue was rather then getting notification out.  

"Furthermore, you failed to report a reportable food to the Reportable Food Registry (RFR) within twenty-four hours of determining that it is reportable (i.e., that there is a reasonable probability that the use of, or exposure to, such animal food will cause serious adverse health consequences or death to animals).5 Failure to submit a required reportable food report is a prohibited act."

"You tried to justify not filing an RFR while you asked the lab to reanalyze and provide the actual amount of monensin present in the sample and continued to assess with your nutritionists, veterinarians, and published data if the elevated level of ionophores would result in an animal health issue. However, this feed was not formulated to contain any monensin (an ionophore) and you were already aware the animals appeared to have died of ionophore toxicity."

As for the improper mixing issues:

Your root cause investigation found the source of the monensin to be the weighed and staged (b)(4) of monensin intended for the next product, Accuration Finisher 44 R227. Your mixing operator occasionally combines (b)(4) from (b)(4) pallets onto a single pallet to minimize time spent moving the ingredients to the mixer. In this instance, you determined the operator combined (b)(4) from the (b)(4) different work orders, then removed all the barcode tags from all staged (b)(4) and placed them near the scanner so they would be accessible when he was ready to scan them. This action left all the micro-ingredients for (b)(4) products unidentified, causing the operator to erroneously add the monensin to the incorrect product. 

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/nutra-blend-llc-subsidiary-land-olakes-651174-05222023
Nutra Blend, LLC subsidiary of Land O’Lakes
MARCS-CMS 651174 — MAY 22, 2023

Product:  Animal & Veterinary  Drugs  Food & Beverages

Recipient:
Ms. Lisa Deverell
President, Purina Animal Nutrition; Executive Vice President, Land O’ Lakes, Inc.
Nutra Blend, LLC subsidiary of Land O’Lakes
4001 Lexington Avenue North
Arden Hills, MN 55126
United States

Issuing Office:
Division of Human and Animal Food Operations West II
United States

May 22, 2023

WARNING LETTER

CMS # 651174
Dear Ms. Deverell,

The U.S. Food and Drug Administration (FDA) conducted an inspection of your licensed medicated feed mill, located at 1609 19th Street SW, Mason City, IA 50401 from December 12 through December 16, 2022, in response to a Reportable Food Registry (RFR) report involving several calf illnesses and deaths after consuming your medicated cattle feed (Purina Rangeland Calf Creep 14 B68 Medicated, lot # 101022). Your lab analyses of feed samples you collected from the customer and your retain sample identified the presence of an unintended drug ingredient, the ionophore monensin, in lot # 101022. The results from the feed samples, the farm’s veterinarian’s statement, and the necropsy reports from the calves that consumed this feed indicate the calves died from ionophore toxicity. You subsequently initiated a recall of this cattle feed on December 7, 2022.

During the inspection, FDA’s Investigator found evidence of a significant violation of the Current Good Manufacturing Practice for Medicated Feeds requirements found in Title 21, Code of Federal Regulations, Part 225 (21 CFR Part 225). Failure of a medicated feed mill to comply with these requirements causes your medicated feed to be adulterated.1 The doing of any act to a food or drug after shipment of the food or drug and/or its components in interstate commerce and while the food or drug is held for sale (whether or not the first sale) that results in the food or drug being adulterated or misbranded is a prohibited act.2

Additionally, the inspection found evidence of a significant violation of the Current Good Manufacturing Practice, Hazard Analysis, and Risk-Based Preventive Controls for Food for Animals requirements found in Title 21, Code of Federal Regulations, Part 507 (21 CFR Part 507) which causes your products to be adulterated.3 Failure of the owner, operator, or agent in charge of a covered facility to comply with the preventive controls requirements of 21 CFR Part 507 (located in subparts A, C, D, E, and F of Part 507) is a prohibited act.4

Furthermore, you failed to report a reportable food to the Reportable Food Registry (RFR) within twenty-four hours of determining that it is reportable (i.e., that there is a reasonable probability that the use of, or exposure to, such animal food will cause serious adverse health consequences or death to animals).5 Failure to submit a required reportable food report is a prohibited act.6

You may find FDA’s regulations and the FD&C Act through links on FDA’s homepage at http://www.fda.gov.

At the close of the inspection, you were issued a Form FDA 483, Inspectional Observations. We acknowledge your written response dated January 04, 2023. We have reviewed your response and address your corrective actions below in relation to each of the noted violations.

Current Good Manufacturing Practice (CGMP) for Medicated Feeds Requirements
As a manufacturer of medicated feed for which an approved medicated feed mill license is required, your facility is subject to the CGMP for Medicated Feeds requirements found in 21 CFR 225.10 – 225.115. During the inspection of your facility, the FDA Investigator identified a significant violation of these requirements:

1. You did not properly identify and control drugs in the mixing areas to maintain their integrity and identity as required by 21 CFR 225.42(b)(4).

You removed all the barcode tags from the (b)(4) containing micro-ingredients (including drugs) on the pallet at the mixer, causing the micro-ingredients to be unidentified. Your Purina Rangeland Calf Creep 14 B68 Medicated, lot # 101022 was formulated to contain the ionophore lasalocid and no other drugs. However, the laboratory test results from both your sample collected from the farm where the deaths occurred and from your retain sample of Purina Rangeland Calf Creep 14 B68 Medicated, lot # 101022 showed the presence of monensin. Your root cause investigation found the source of the monensin to be the weighed and staged (b)(4) of monensin intended for the next product, Accuration Finisher 44 R227. Your mixing operator occasionally combines (b)(4) from (b)(4) pallets onto a single pallet to minimize time spent moving the ingredients to the mixer. In this instance, you determined the operator combined (b)(4) from the (b)(4) different work orders, then removed all the barcode tags from all staged (b)(4) and placed them near the scanner so they would be accessible when he was ready to scan them. This action left all the micro-ingredients for (b)(4) products unidentified, causing the operator to erroneously add the monensin to the incorrect product. Your analysis of your retain sample for the next product, Accuration Finisher 44 R227, lot # 10122, confirmed it was lower in monensin than the labeled potency.

Evaluation of your response:

In your written response to the Form FDA 483, you provided updated SOP, “(b)(4)” for the addition of a new barcode system and labeling of (b)(4) for both non-medicated and medicated pre-weigh micro-ingredients. In addition, you provided updated SOP, “(b)(4)” for the batch mixing process which includes the new addition of barcode scanning and allows for only (b)(4) to be staged at a time. Training sign-off sheets for both procedures were provided as well. However, we are unable to fully evaluate your corrective actions since you did not provide supporting documentation to demonstrate the promised corrections have been consistently implemented. We encourage you to provide additional evidence, such as photographs of labeled pre-weigh ingredients or other documentation demonstrating the consistent implementation of your updated procedures.

Hazard Analysis and Risk-Based Preventive Controls Requirements

Your animal food facility is subject to the hazard analysis and risk-based preventive controls requirements found in 21 CFR part 507, subparts A, C, D, E, and F. During the inspection of your facility, the FDA investigator identified a significant violation of these requirements:

2. You failed to sufficiently assess the probability that a hazard will occur in the absence of a preventive control, as required by 21 CFR 507.33(c)(1).

Your process hazard analysis identified the probability of accidentally adding certain drug ingredients (including lasalocid and monensin) to the wrong batches as “low” based on your firm’s prior history, but you failed to consider that you recently made a major change in your process for staging ingredients that significantly increased this risk. As a result of this change, your prerequisite program failed to prevent a "Drug/Additive of Concern” from being added to the wrong formulation.

Your “Drug & Additives of Concern Hazard Assessment – Mason City, IA” identifies lasalocid and monensin as drugs of concern that may cause toxicity in horses, ostriches, camels, rabbits, alpacas, llamas, and potentially deer.

You determined these drugs are not high severity drugs of concern for your process hazard analysis because you do not manufacture feed for the aforementioned species. Your process hazard analysis, dated October 26, 2022, identifies “Introduction of Drug/Additive of Concern from Adding the Wrong Ingredient – NOT Identified as High Severity” as a process hazard at the mixing step with a low likelihood based on an incidence history of limited occurrence of adding the wrong ingredient and medium severity of illness or injury to animals if the hazard were to occur. During the inspection, you indicated the hazard is being addressed by your prerequisite manufacturing control program. You identified your “Mixing Program,” dated October 14, 2015, as justification for deciding a preventive control is not needed to control this hazard of wrongly adding a drug of concern during mixing.

However, the "Mixing Program" had not been revised after the change in your facility’s ownership in February 2022, which resulted in a change in the process flow for weighing and staging micro-ingredients, including drugs. After the change in ownership, your firm separated the medicated and unmedicated micro-ingredient storage away from the mixer. This separation increased the risk of introducing a drug or additive of concern at the mixing step because your operator can stage several batches of various micro-ingredients in the warehouse, move them to the mixer when ready to mix them, and remove their barcode tags leaving the batches of micro-ingredients without identification.

Your firm's process hazard analysis, dated October 26, 2022, relied on the prior history of your old process and, therefore, failed to evaluate the probability the hazard of “Introduction of Drug/Additive of Concern from Adding the Wrong Ingredient – NOT Identified as High Severity” would occur with your new process in the absence of a preventive control. The new process was inadequate to reduce the probability the hazard will occur, as evidenced by the inadvertent addition of monensin into the Purina Rangeland Calf Creep 14 B68 Medicated lot # 101022 and the subsequent recall by your firm.

Evaluation of your response:

In your written response to the Form FDA 483, you stated your firm made updates to “(b)(4)” to reflect changes made to your process flow in February 2022. In addition, you implemented a new procedure, “(b)(4),” for the labeling of hand-add containers for both non-medicated and medicated pre-weigh micro-ingredients. Training has been completed for both procedures. However, we are unable to fully evaluate your corrective actions since you did not provide supporting documentation to demonstrate the promised corrections have been implemented.

Reportable Food Registry (RFR)

3. You failed to report a reportable food to the RFR within 24 hours of determining that an article of food is a reportable food as required by section 417(d)(1)(A) of the FD&C Act.

On October 24, 2022, a customer notified you that a medicated animal feed you manufactured, Purina Rangeland Calf Creep 14 B68 Medicated, lot # 101022, had been implicated in multiple illnesses and deaths of calves that had consumed it. On November 14, 2022, you received the preliminary veterinary diagnostic report which included a Veterinarian’s Statement from the farm’s veterinarian, necropsy and histopathology results, and ionophore panel results for feed samples collected by the farm’s veterinarian. The veterinary pathology report concluded the calves examined likely died of ionophore toxicity and the feed analysis found the presence of monensin (256.4 ppm) and lasalocid (61.3 ppm). Additionally, your firm submitted samples of your beef feed collected from the customer, as well as your retain sample of Purina Rangeland Calf Creep 14 B68 Medicated, lot # 101022, to a third-party diagnostic lab for ionophore analysis. On December 2, 2022, you received the reports for your retain sample and the farm sample, which indicated the presence of monensin at >100 ppm. However, you did not file a RFR until December 7, 2022. Additionally, in your RFR, you listed the date the other firm in the supply chain (i.e., your customer) notified you about the reportable food (“Date notified”) as December 6, 2022.

Evaluation of your response:

Your response implied you did not file a RFR once you received the veterinary diagnostic report from the farm’s veterinarian on November 14, 2022, because you were unsure if the “Pruina [sic] Beef feed” identified in the veterinarian’s statement was your Purina Rangeland Calf Creep 14 B68 Medicated feed. You also explained that you received your retain sample result on December 2, 2022, but it did not provide the actual level of monensin and only showed it was “>100 ppm.”

You tried to justify not filing an RFR while you asked the lab to reanalyze and provide the actual amount of monensin present in the sample and continued to assess with your nutritionists, veterinarians, and published data if the elevated level of ionophores would result in an animal health issue. However, this feed was not formulated to contain any monensin (an ionophore) and you were already aware the animals appeared to have died of ionophore toxicity.

The term “reportable food” means an article of food for which there is a reasonable probability [emphasis added] that the use of, or exposure to, such an article of food will cause serious adverse health consequences or death to humans or animals.7 A firm's report of a reportable food event is not considered an admission that the food involved is adulterated or caused or contributed to a death, serious injury, or serious illness, but is considered a safety report under section 756 of the FD&C Act [21 U.S.C. § 379v].

Conclusion

This letter is not intended to be an all-inclusive statement of violations that may exist at your facility or in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law and FDA regulations.

This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may lead to legal or regulatory action, including without limitation, seizure and injunction.

Additionally, FDA would like to address the following:

1. During the inspection, it was noted that your hazard analysis did not identify mycotoxin formation in grains at ingredient storage. In your written response to the Form FDA 483, you provided your firm’s mitigation procedures for mycotoxin formation in grains during storage. However, you did not provide documentation that you have identified mycotoxins as a known or reasonably foreseeable hazard and evaluated the hazard to assess the severity of the illness or injury if the hazard were to occur and the probability that the hazard would occur in the absence of a preventive control, for the purpose of determining whether a preventive control is required. (See 21 CFR 507.33.)

2. As noted above, you went through a change in ownership in February 2022, which resulted in a change in the process flow for weighing and staging micro-ingredients. You must conduct a reanalysis of your food safety plan whenever a significant change in the activities conducted at your facility creates a reasonable potential for a new hazard or creates a significant increase in a previously identified hazard. (21 CFR 507.50(b)(1).)

For more information about FDA’s current thinking on the requirements of 21 CFR Part 507, see:

Guidance for Industry #235: “Current Good Manufacturing Practice Requirements for Food for Animals” https://www.fda.gov/media/97464/download

Guidance for Industry #245: “Hazard Analysis and Risk-Based Preventive Controls for Food for Animals” https://www.fda.gov/media/110477/download

Guidance for Industry #246: “Hazard Analysis and Risk-Based Preventive Controls for Food for Animals: Supply Chain Program” https://www.fda.gov/media/113923/download

Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. If you cannot complete corrective actions within fifteen (15) working days, state the reason for the delay and the time frame within which you will complete the correction. If you believe that you have complied with the FD&C Act and FDA regulations, include your reasoning and any supporting information for our consideration.

Please send your firm’s written response to Kevin A. Beavers, Compliance Officer, U.S. Food and Drug Administration, 8050 Marshall Dr., Suite 205, Lenexa, KS 66214. If you have any questions about this letter, please contact Compliance Officer Beavers at 417-873-9455 Ext 102.

Sincerely,
/S/
LaTonya M. Mitchell, Ph.D.
Program Division Director
Office of Human and Animal Foods
West Division II


Cc: Wesley W. Fiddelke, Plant Manager, Nutra Blend at wwfiddelke@landolakes.com