The company did not have a Preventive Control Plan for its animal feed product. There were GMP issues including the lack of control focused on mycotoxins. There were also issues with separation of feeds for different animal types. And issues associated with the proper control of medications used in feed.
https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/appleton-city-feed-service-llc-662279-11012023
Appleton City Feed Service LLC
MARCS-CMS 662279 — NOVEMBER 01, 2023
Recipient:
Ms. Tamera S. Smith
Owner
Appleton City Feed Service LLC
302 W. 4th Street
Appleton City, MO 64724-1406
United States
Issuing Office:
Division of Human and Animal Food Operations West II
United States
November 1, 2023
WARNING LETTER
CMS # 662279
Dear Ms. Smith,
The U.S. Food and Drug Administration (FDA) conducted an inspection of your non-FDA licensed medicated feed mill located at 302 W. 4th Street, Appleton City, Missouri, from April 27 through May 22, 2023.
The inspection revealed evidence of significant violations 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 cause your products to be adulterated.1 Furthermore, 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 is a prohibited act.2
In addition, the inspection revealed evidence of significant violations of the requirements for animal feed containing a Veterinary Feed Directive (VFD) drug (VFD feed), 21 CFR 558.6. Failure of a facility to comply with the VFD requirements causes the resulting VFD feed to be unsafe within the meaning of the FD&C Act.3 A drug is adulterated if it is an animal feed bearing or containing a new animal drug and the animal feed is unsafe.4
Further, the failure of a facility to follow the VFD requirements causes the VFD feed to no longer be exempt from the requirement that its labeling bear adequate directions for use and as a result, the drug is misbranded if it does not bear adequate directions for use.5
Also, the inspection revealed evidence of significant violations of the Current Good Manufacturing Practice (CGMP) for Medicated Feeds requirements, 21 CFR Part 225. Failure of a medicated feed mill to comply with these requirements causes your medicated and non-medicated feed to be adulterated.6
Lastly, the inspection revealed that you were using new animal drugs in combinations that are contrary to the New Animal Drug Application (NADA) approvals. The resulting medicated feed is unsafe because the new animal drug was not used in conformance with the drug approval.7 As a result, the new animal drug is adulterated.8
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.9
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 responses dated June 16, 2023, and July 11, 2023. We have reviewed your responses and address them below in relation to each of the noted violations.
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 Investigators observed evidence of a significant violation of these requirements:
1. You did not prepare, or have prepared, and did not implement a written food safety plan, as required by 21 CFR 507.31(a). The preparation of the food safety plan must be overseen by your preventive controls qualified individual (PCQI), as required by 21 CFR 507.31(b), and must include the following, in accordance with 21 CFR 507.31(c):
a. The written hazard analysis as required by 21 CFR 507.33(a)(2);
b. The written preventive controls as required by 21 CFR 507.34(b);
c. The written supply-chain program as required by subpart E of 21 CFR Part 507;
d. The written recall plan as required by 21 CFR 507.38(a)(1);
e. The written procedures for monitoring the implementation of the preventive controls as required by 21 CFR 507.40(a);
f. The written corrective action procedures as required by 21 CFR 507.42(a)(1); and
g. The written verification procedures as required by 21 CFR 507.49(b).
Specifically, during the inspection you stated that you have not conducted a hazard analysis, you do not have a PCQI, and you do not have a written food safety plan.
Evaluation of your response:
In your response dated June 16, 2023, you stated you will establish a written food safety plan. However, you have not provided your food safety plan or any implementation documentation, nor have you provided a timeline for completion and consistent implementation of a food safety plan. Therefore, we are unable to evaluate the adequacy of your response. We encourage you to provide us with your food safety plan and implementation documentation in follow-up correspondence.
Current Good Manufacturing Practice (CGMP) Requirements
Your animal food facility is subject to the CGMP requirements found in 21 CFR Part 507, Subparts A, B, and F. During the inspection of your facility, the FDA Investigators observed evidence of significant violations of these requirements, which included:
2. You failed to evaluate and use raw materials and other ingredients susceptible to contamination with mycotoxins or other natural toxins in a manner that does not result in animal food that can cause injury or illness to animals or humans, as required by 21 CFR 507.25(b)(2).
Specifically, you receive, store, and use grain and grain co-products susceptible to mycotoxin contamination, including corn, dried distiller’s grains, oats, and soybean meal, to make animal food at your facility. However, you do not have procedures, conduct testing, or have any processes in place to determine whether mycotoxins such as aflatoxin, fumonisin, or deoxynivalenol (DON/vomitoxin) are present in the ingredients you receive, store, and use in your animal food. During the inspection, you confirmed that you do not evaluate incoming ingredients for mycotoxins, including that you do not test for them.
Evaluation of your response:
In your response dated June 16, 2023, you stated you will establish a process to test for mycotoxins and other toxins and look into purchasing test kits. However, you did not provide any documentation indicating you have established or are consistently implementing procedures for sampling and testing your grain ingredients for mycotoxins nor have you provided a timeline for completion of your corrective actions. Therefore, we are unable to evaluate the adequacy of your response. We encourage you to provide documentation of your corrective actions in follow-up correspondence.
3. You did not take adequate precautions so that plant operations do not contribute to contamination of animal food, as required by 21 CFR 507.25(a)(5).
Specifically, you did not take adequate precautions such as flushing your equipment and/or sequencing batches of animal food, so that your feed mill operations would not contribute to the contamination of animal food. For example, your firm produces food for cattle with levels of copper that could be toxic to other species for which you also produce animal food, such as sheep. A review of records revealed that on (b)(4), your firm manufactured (b)(4) batches of cattle food, one of which contained copper, prior to manufacturing a batch of sheep food, but you did not know which cattle food was made prior to the sheep food. To add to the problem, your firm did not conduct any flushing between mixing batches of different foods, despite the fact that your mixer does not fully empty, leaving approximately (b)(4) of food from each batch, some of which is then incorporated into the subsequent batch. The failure to take flushing and sequencing actions can potentially cause carryover of copper to the sheep food. Elevated levels of copper in sheep food could cause serious adverse health consequences or death in sheep.
As another example, on (b)(4), you manufactured a non-medicated horse food that included (b)(4) of an unlabeled, customer-provided, mineral premix with unknown ingredients. You manufactured this horse food immediately before you manufactured a sheep food, but you did not take adequate precautions, such as flushing, so that your use of the unidentified premix would not contribute to the contamination of the sheep food.
Evaluation of your response:
Your response dated July 11, 2023, stated, “[T]o avoid cross contamination of feeds to different species a flush will be performed in the mixer and recorded on [the] scale sheet . . .”. You also stated you will start requiring a label on unlabeled premixes from customers. However, because you did not provide any documentation to demonstrate that your corrections have been completed and are consistently implemented, we are unable to evaluate your corrections. We encourage you to provide us with documentation of your corrections in follow-up correspondence.
4. You failed to take effective measures to exclude pests from the manufacturing, processing, packing, and holding areas and to protect against contamination of animal food by pests, as required by 21 CFR 507.19(e).
Specifically, on April 27 through May 11, 2023, the FDA Investigator observed the following pest activity inside your facility:
a. Apparent rodent excreta in and around bagged mineral ingredients and medicated feeds. Additionally, apparent rodent excreta were found inside a tote used to store Type A medicated articles and Type B medicated feeds.
b. Apparent animal gnaw holes on bags of finished medicated feed.
c. Animal tracks in spilled ingredients throughout the drug mixing and storage room.
Evaluation of your response:
In your response dated July 11, 2023, you stated you will store drug ingredients in containers, and you have placed rodent traps throughout your facility. However, you did not provide documentation to demonstrate that your corrections have been completed and are consistently implemented. Therefore, we are unable to evaluate the adequacy of your corrective actions. We encourage you to provide us with documentation of your corrective actions in future correspondence.
Veterinary Feed Directive (VFD) Requirements
As a VFD feed manufacturer and distributor, your facility is subject to the VFD requirements found in 21 CFR 558.6. During the inspection of your facility, the FDA Investigators observed significant violations of these requirements, which include:
5. You did not use and label a VFD drug or combination VFD drug in feed in accordance with the approved, conditionally approved, or indexed conditions of use, as required by 21 CFR 558.6(a)(3).
Specifically, between November 23, 2022 and December 9, 2022 you manufactured and delivered to your customer (b)(4) different batches of feed under a VFD order issued on September 22, 2022 that was written for Aureomycin S700 (chlortetracycline and sulfamethazine) with a final concentration of (b)(4) of chlortetracycline and sulfamethazine in the finished feed. You added monensin to each of the (b)(4) batches. Monensin is not approved for use in combination with chlortetracycline and sulfamethazine.10
Evaluation of your response:
Your response dated July 11, 2023, states you will, “Use Code of Federal Reg Title 21.” You did not elaborate on how you intend to use the federal regulations or provide any documentation of any corrective actions you have taken. Therefore, we are unable to evaluate your corrections. We encourage you to provide us with documentation of your corrections in follow-up correspondence.
6. You distributed an animal feed containing a VFD drug or combination VFD drug that did not conform comply with the terms of the VFD, as required by 21 CFR 558.6(c)(2).
Specifically, on the following occasions, you manufactured and distributed VFD feeds containing Aureomycin (chlortetracycline) at a concentration and/or a VFD drug combination that did not comply with the terms of the VFD:
a. You received VFD order (b)(4) for a free choice cattle feed to contain (b)(4) chlortetracycline. The VFD only authorized the use of chlortetracycline and did not authorize the use of any drug combinations.
i. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing (b)(4) chlortetracycline, which is only (b)(4) of the specified concentration of (b)(4). Additionally, you added monensin although drug combinations were not authorized by the VFD.
ii. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing (b)(4) chlortetracycline, which is only (b)(4) of the specified concentration of (b)(4). Additionally, you added monensin although drug combinations were not authorized by the VFD.
b. You received VFD order (b)(4) for a cattle feed to contain (b)(4) chlortetracycline. The VFD only authorized the use of chlortetracycline and did not authorize the use of any drug combinations.
i. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing (b)(4) chlortetracycline, which is only (b)(4) of the specified concentration of (b)(4). Additionally, you added monensin although drug combinations were not authorized by the VFD.
ii. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing (b)(4) chlortetracycline, which is only (b)(4) of the specified concentration of (b)(4). Additionally, you added monensin although drug combinations were not allowed by the VFD.
iii. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing chlortetracycline. You added monensin, although drug combinations were not allowed by the VFD.
c. You received VFD order (b)(4) for a cattle feed to contain (b)(4) chlortetracycline.
i. On (b)(4), per weigh ticket (b)(4), you manufactured two batches of VFD feed. The first batch consisted of (b)(4) pounds of VFD feed that contained (b)(4) chlortetracycline, which is (b)(4) of the specified concentration of (b)(4).
ii. The second batch consisted of (b)(4) pounds of VFD feed that contained (b)(4) chlortetracycline, which is (b)(4) of the specified concentration of (b)(4).
Also, specifically with regard to the requirement in 21 CFR 558.6(c)(2) that you distribute feed containing VFD drugs labeled in conformity with the approved, conditionally approved, or indexed conditions of use for each drug: You provide your customers with invoices or weigh tickets that include the formulated weights for each ingredient in the feed but do not include the indication for use, feeding directions, cautions, or warnings. You stated that you sometimes send the Type A medicated article tag or the tag from the Type B medicated feed with your feed but that “(b)(4)” your customer is not there to receive the paperwork and your drivers do not leave the paperwork.
Evaluation of your response:
Your response dated July 11, 2023, states you will be “taking a closer look at the VFD to follow mixing guidelines.” You did not elaborate on how you intend ensure the VFD feed is manufactured and labeled in conformance with the approved use of the drug and the VFD authorizing the distribution or provide documentation of any corrective actions you have taken. Therefore, we are unable to evaluate your corrections. We encourage you to provide us with documentation of your corrections in follow-up correspondence.
7. You distributed feed containing VFD drugs without prominently and conspicuously displaying the required cautionary statement: “Caution: Federal law restricts medicated feed containing this veterinary drug to use by or on the order of a licensed veterinarian,” as required by 21 CFR 558.6(a)(6).
Specifically, as described above, when distributing feed containing VFD drugs, you provide customers with invoices or weigh tickets that do not include the required cautions or warnings.
Misbranded Drug
As outlined above, your facility is not following FDA’s regulations in 21 CFR part 558 and the requirements of section 504 of FD&C Act when distributing, holding, and using VFD drugs and animal feed containing these drugs. The failure of a facility to follow the VFD requirements causes the VFD drug to no longer be exempt from the requirements of section 502(f) of the FD&C Act. Section 502(f)(1) states that a drug is deemed to be misbranded unless its labeling bears adequate directions for use. Thus, your VFD feed labeling must bear adequate directions for use or the drug will be misbranded. You provide your customers with invoices or weigh tickets that include the formulated weights for each ingredient in the feed, including drugs. However, these invoices or weigh tickets do not include any directions for use.
Current Good Manufacturing Practice (CGMP) for Medicated Feeds Requirements
Your facility is required to follow the medicated feed CGMP regulations for non-licensed, medicated animal feed manufacturers found in 21 CFR 225.120-202. During the inspection, the FDA Investigators observed evidence of significant violations of these requirements, which included:
8. You did not establish and use adequate procedures for all equipment used in the production and distribution of medicated feeds to avoid unsafe contamination of medicated and nonmedicated feeds, as required by 21 CFR 225.165.
Specifically, you did not flush, sequence, or use physical means to prevent potential drug carryover into non-medicated feed batches that were manufactured after medicated feeds. On (b)(4), your firm manufactured a medicated feed containing monensin and amprolium, documented on weigh ticket (b)(4). The feed was (b)(4). Feed was observed to be left in the bottom of the mixer and you did not clean the mixer out prior to manufacturing a non-medicated cattle feed. Your manager stated that your firm does not conduct any flushing between mixing batches of different feeds and your mixer does not fully empty, leaving approximately (b)(4) of feed from each batch, some of which is then incorporated into the subsequent batch. Additionally, your feed trucks do not fully empty, and you do not clean out the remaining feed prior to loading a new feed or conduct any sequencing when loading your feed delivery trucks.
Evaluation of your response:
In your response dated July 11, 2023, you stated, “to avoid cross contamination of feeds to different species a flush will be performed in the mixer and recorded on the scale sheet at [that] time.” However, because you did not provide documentation to demonstrate that your corrections have been completed and are being consistently implemented, we are unable to evaluate your corrections. We encourage you to provide us with documentation of your corrections in follow-up correspondence.
9. You did not establish and maintain adequate procedures for the identification, storage, and inventory control (receipt and use) of all Type A medicated articles and Type B medicated feeds intended for use in the manufacture of medicated feeds to aid in assuring the identity, strength, quality, and purity of these drug sources. All Type A medicated articles and Type B medicated feeds must be used in accordance with their labeled mixing directions, as required by 21 CFR 225.142. Specifically,
a. You do not have procedures in place, nor do you document the receipt, storage, or use of Type A medicated articles and Type B medicated feeds. Your manager confirmed that employees do not document the actual weights of ingredients added to the mixer and a drug inventory is not maintained.
b. You do not make a working premix, preblend, or intermediate blend in accordance with the labeled mixing directions for Type A medicated articles Aureomycin Granular A (chlortetracycline), Deracin 50 (chlortetracycline), and Rumensin 90 (monensin) to ensure an adequate mix is performed. The mixing directions on these labels outline intermediate blending steps to be completed prior to mixing into Type C medicated feeds, which you did not follow.
Evaluation of your response:
Your responses dated June 16, 2023, and July 11, 2023, do not include any corrective actions you have taken to address the observations noted above; Therefore, we are unable to evaluate your corrections.
10. You failed to ensure that all deliveries of medicated feeds, whether bagged or in bulk, are adequately labeled to assure that the feed can be properly used as required by 21 CFR 225.180.11
Specifically, you provide your customers with invoices or weigh tickets that include the formulated weights for each ingredient in the feed, including drugs. However, you do not provide labeling to your customers that includes required cautionary statements, feeding instructions, warnings, and information regarding the drug concentration of the feed to assure that the feed can be safely and properly used. For example, you manufacture and distribute medicated feed containing monensin without including labeling bearing the caution statement, “Do not allow horses or other equines access to feed containing monensin. Ingestion of monensin by horses has been fatal.”12 In addition, you do not document which feeds were loaded onto your delivery trucks and you do not document which truck compartment the feed was loaded into.
Evaluation of your response:
Your response dated July 11, 2023, states you will establish labels for finished feeds for your customers and the labels will be “sent to the customer” since customers are not always present at the time of delivery. We are unable to evaluate the adequacy of your response since you did not provide any documentation, such as examples of labels or procedures you have put in place, to show your corrective actions have been completed and implemented.
Unapproved Drug Combinations in Animal Feed
During the inspection, the FDA Investigators found evidence that you were using new animal drugs in combinations that are contrary to the New Animal Drug Application (NADA) approvals. Specifically, the Investigators observed the following:
11. On May 5, 2023, the Investigators observed your manufacture of a medicated feed in accordance with weigh ticket (b)(4). You added (b)(4) bags of amprolium and (b)(4) bags of monensin to the mixer while manufacturing the feed. The combination of amprolium and monensin is not FDA approved.13
12. As described in violation #5 above, the FDA Investigators observed evidence that on (b)(4) occasions that you used monensin in medicated cattle feed in combination with chlortetracycline and sulfamethazine, which is not an FDA approved combination for cattle feed.14
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 you comply 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 action, including without limitation, seizure and injunction.
We have the following comments:
1. The FDA Investigators observed that you used the over-the-counter drug amprolium in medicated feed for sheep, which is a “minor species” as defined in the FD&C Act. Amprolium is not FDA approved for use in sheep feed.15 The Investigators also observed that you used the over-the-counter drugs monensin (b)(4) or lasalocid in feed for goats, a minor species. Monensin is approved for use in goat feed at a maximum level of 20g/ton16 and lasalocid is not approved for use in goat feed.17 Therefore, these uses would be an extra-label use of the animal drug in your feed, which is illegal.18 However, under certain circumstances, FDA may decide not to bring enforcement action against this illegal use. We recommend you familiarize yourself with those circumstances, which are described in FDA’s Compliance Policy Guide Sec. 615.115, “Extralabel Use of Medicated Feeds for Minor Species,” available at https://www.fda.gov/media/71960/download. The circumstances FDA considers include, in part: whether the feed is for a minor species, whether there is express prior written recommendation and oversight by a licensed veterinarian, whether the feed is formulated, manufactured, and labeled appropriately, and whether you have prepared and maintained records as required.
2. 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/regulatory-information/search-fda-guidance-documents/cvm-gfi-235-current-good-manufacturing-practice-requirements-food-animals
• Guidance for Industry #245, “Hazard Analysis and Risk-Based Preventive Controls for Food for Animals”
• https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-245-hazard-analysis-and-risk-based-preventive-controls-food-animals
3. For more information about FDA’s current thinking on the requirements of 21 CFR Part 225 and VFDs, see:
• Medicated Feeds | FDA
• https://www.fda.gov/animal-veterinary/animal-food-feeds/medicated-feeds
• Veterinary Feed Directive (VFD) | FDA
• https://www.fda.gov/animal-veterinary/development-approval-process/veterinary-feed-directive-vfd
• Drugs with Veterinary Feed Directive (VFD) Marketing Status | FDA
• https://www.fda.gov/animal-veterinary/development-approval-process/drugs-veterinary-feed-directive-vfd-marketing-status
• CVM GFI #120 Veterinary Feed Directive Regulation Questions and Answers | FDA
• https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-120-veterinary-feed-directive-regulation-questions-and-answers
• Blue Bird Labels | FDA
• https://www.fda.gov/animal-veterinary/medicated-feeds/blue-bird-labels) A VFD authorizes a customer to receive a Type B or Type C medicated feed. If a customer receives a Type B medicated feed, the customer must follow appropriate mixing directions so that the resulting Type C medicated feed conforms to the VFD drug approval and the VFD authorizing the use of the VFD feed. This website has representative labeling with mixing instructions for Type B medicated feeds. If a customer receives a type C medicated feed, the customer must have information such as feeding instructions and warnings in order to use the VFD feed safely. This website includes instructions, “Searching for Blue Bird Labels,” and a link to a database containing FDA approved representative (“Blue Bird”) labeling that feed mills use to prepare adequate labeling for their VFD feeds.
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 timeframe within which you will complete the correction. If you believe you have complied with the FD&C Act and FDA regulations, include your reasoning and any supporting information for our consideration.
Please send your written response to Kevin A. Beavers, Compliance Officer, U.S. Food and Drug Administration, 8050 Marshall Dr., Suite 205, Lenexa, Kansas 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
_____________________
1 See Section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), [21 U.S.C. § 342(a)(4)] and 21 CFR 507.1(a)(1)(ii).
2 See Section 301(uu) of the FD&C Act [21 U.S.C. § 331(uu)].
3 See Section 512(a)(2) of the FD&C Act [21 U.S.C. § 360b(a)(2)].
4 See Section 501(a)(6) of the FD&C Act 21 U.S.C. § 351(a)(6)]and 21 CFR 558.6(c)(2) and 21 CFR 558.6(a)(3).
5 See Section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]; see also section 504(a)(1) of the FD&C Act [21 U.S.C. § 354(a)(1)].
6 See Section 501(a)(2)(B) of the FD&C Act [21 U.S.C. § 351(a)(2)(B)] and 21 CFR 225.1(b)(1).
7 See Section 512(a)(2)(A) of the FD&C Act [21 U.S.C. § 360b(a)(2)(A)].
8 See Section 501(a)(6) of the FD&C Act [21 U.S.C. § 351(a)(6)].
9 See Section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].
10 See 21 CFR 558.140.
11 See also 21 CFR 507.27(b).
12 See 21 CFR 558.355(d)(6).
13 See 21 CFR 558.55, 21 CFR 558.58, and 21 CFR 558.355 for approved uses of amprolium and monensin in animal food.
14 See 21 CFR 558.355 and 21 CFR 558.140 for approved uses of monensin and for chlortetracycline in combination with sulfamethazine, respectively.
15 See 21 CFR 558.55 for approved uses of amprolium.
16 See 21 CFR 558.355(f)(6).
17 See 21 CFR 558.311 for approved uses of lasalocid.
18 See 21 CFR 530.11(b).
i. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing (b)(4) chlortetracycline, which is only (b)(4) of the specified concentration of (b)(4). Additionally, you added monensin although drug combinations were not authorized by the VFD.
ii. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing (b)(4) chlortetracycline, which is only (b)(4) of the specified concentration of (b)(4). Additionally, you added monensin although drug combinations were not allowed by the VFD.
iii. On (b)(4), per weigh ticket (b)(4), you manufactured (b)(4) pounds of VFD feed containing chlortetracycline. You added monensin, although drug combinations were not allowed by the VFD.
c. You received VFD order (b)(4) for a cattle feed to contain (b)(4) chlortetracycline.
i. On (b)(4), per weigh ticket (b)(4), you manufactured two batches of VFD feed. The first batch consisted of (b)(4) pounds of VFD feed that contained (b)(4) chlortetracycline, which is (b)(4) of the specified concentration of (b)(4).
ii. The second batch consisted of (b)(4) pounds of VFD feed that contained (b)(4) chlortetracycline, which is (b)(4) of the specified concentration of (b)(4).
Also, specifically with regard to the requirement in 21 CFR 558.6(c)(2) that you distribute feed containing VFD drugs labeled in conformity with the approved, conditionally approved, or indexed conditions of use for each drug: You provide your customers with invoices or weigh tickets that include the formulated weights for each ingredient in the feed but do not include the indication for use, feeding directions, cautions, or warnings. You stated that you sometimes send the Type A medicated article tag or the tag from the Type B medicated feed with your feed but that “(b)(4)” your customer is not there to receive the paperwork and your drivers do not leave the paperwork.
Evaluation of your response:
Your response dated July 11, 2023, states you will be “taking a closer look at the VFD to follow mixing guidelines.” You did not elaborate on how you intend ensure the VFD feed is manufactured and labeled in conformance with the approved use of the drug and the VFD authorizing the distribution or provide documentation of any corrective actions you have taken. Therefore, we are unable to evaluate your corrections. We encourage you to provide us with documentation of your corrections in follow-up correspondence.
7. You distributed feed containing VFD drugs without prominently and conspicuously displaying the required cautionary statement: “Caution: Federal law restricts medicated feed containing this veterinary drug to use by or on the order of a licensed veterinarian,” as required by 21 CFR 558.6(a)(6).
Specifically, as described above, when distributing feed containing VFD drugs, you provide customers with invoices or weigh tickets that do not include the required cautions or warnings.
Misbranded Drug
As outlined above, your facility is not following FDA’s regulations in 21 CFR part 558 and the requirements of section 504 of FD&C Act when distributing, holding, and using VFD drugs and animal feed containing these drugs. The failure of a facility to follow the VFD requirements causes the VFD drug to no longer be exempt from the requirements of section 502(f) of the FD&C Act. Section 502(f)(1) states that a drug is deemed to be misbranded unless its labeling bears adequate directions for use. Thus, your VFD feed labeling must bear adequate directions for use or the drug will be misbranded. You provide your customers with invoices or weigh tickets that include the formulated weights for each ingredient in the feed, including drugs. However, these invoices or weigh tickets do not include any directions for use.
Current Good Manufacturing Practice (CGMP) for Medicated Feeds Requirements
Your facility is required to follow the medicated feed CGMP regulations for non-licensed, medicated animal feed manufacturers found in 21 CFR 225.120-202. During the inspection, the FDA Investigators observed evidence of significant violations of these requirements, which included:
8. You did not establish and use adequate procedures for all equipment used in the production and distribution of medicated feeds to avoid unsafe contamination of medicated and nonmedicated feeds, as required by 21 CFR 225.165.
Specifically, you did not flush, sequence, or use physical means to prevent potential drug carryover into non-medicated feed batches that were manufactured after medicated feeds. On (b)(4), your firm manufactured a medicated feed containing monensin and amprolium, documented on weigh ticket (b)(4). The feed was (b)(4). Feed was observed to be left in the bottom of the mixer and you did not clean the mixer out prior to manufacturing a non-medicated cattle feed. Your manager stated that your firm does not conduct any flushing between mixing batches of different feeds and your mixer does not fully empty, leaving approximately (b)(4) of feed from each batch, some of which is then incorporated into the subsequent batch. Additionally, your feed trucks do not fully empty, and you do not clean out the remaining feed prior to loading a new feed or conduct any sequencing when loading your feed delivery trucks.
Evaluation of your response:
In your response dated July 11, 2023, you stated, “to avoid cross contamination of feeds to different species a flush will be performed in the mixer and recorded on the scale sheet at [that] time.” However, because you did not provide documentation to demonstrate that your corrections have been completed and are being consistently implemented, we are unable to evaluate your corrections. We encourage you to provide us with documentation of your corrections in follow-up correspondence.
9. You did not establish and maintain adequate procedures for the identification, storage, and inventory control (receipt and use) of all Type A medicated articles and Type B medicated feeds intended for use in the manufacture of medicated feeds to aid in assuring the identity, strength, quality, and purity of these drug sources. All Type A medicated articles and Type B medicated feeds must be used in accordance with their labeled mixing directions, as required by 21 CFR 225.142. Specifically,
a. You do not have procedures in place, nor do you document the receipt, storage, or use of Type A medicated articles and Type B medicated feeds. Your manager confirmed that employees do not document the actual weights of ingredients added to the mixer and a drug inventory is not maintained.
b. You do not make a working premix, preblend, or intermediate blend in accordance with the labeled mixing directions for Type A medicated articles Aureomycin Granular A (chlortetracycline), Deracin 50 (chlortetracycline), and Rumensin 90 (monensin) to ensure an adequate mix is performed. The mixing directions on these labels outline intermediate blending steps to be completed prior to mixing into Type C medicated feeds, which you did not follow.
Evaluation of your response:
Your responses dated June 16, 2023, and July 11, 2023, do not include any corrective actions you have taken to address the observations noted above; Therefore, we are unable to evaluate your corrections.
10. You failed to ensure that all deliveries of medicated feeds, whether bagged or in bulk, are adequately labeled to assure that the feed can be properly used as required by 21 CFR 225.180.11
Specifically, you provide your customers with invoices or weigh tickets that include the formulated weights for each ingredient in the feed, including drugs. However, you do not provide labeling to your customers that includes required cautionary statements, feeding instructions, warnings, and information regarding the drug concentration of the feed to assure that the feed can be safely and properly used. For example, you manufacture and distribute medicated feed containing monensin without including labeling bearing the caution statement, “Do not allow horses or other equines access to feed containing monensin. Ingestion of monensin by horses has been fatal.”12 In addition, you do not document which feeds were loaded onto your delivery trucks and you do not document which truck compartment the feed was loaded into.
Evaluation of your response:
Your response dated July 11, 2023, states you will establish labels for finished feeds for your customers and the labels will be “sent to the customer” since customers are not always present at the time of delivery. We are unable to evaluate the adequacy of your response since you did not provide any documentation, such as examples of labels or procedures you have put in place, to show your corrective actions have been completed and implemented.
Unapproved Drug Combinations in Animal Feed
During the inspection, the FDA Investigators found evidence that you were using new animal drugs in combinations that are contrary to the New Animal Drug Application (NADA) approvals. Specifically, the Investigators observed the following:
11. On May 5, 2023, the Investigators observed your manufacture of a medicated feed in accordance with weigh ticket (b)(4). You added (b)(4) bags of amprolium and (b)(4) bags of monensin to the mixer while manufacturing the feed. The combination of amprolium and monensin is not FDA approved.13
12. As described in violation #5 above, the FDA Investigators observed evidence that on (b)(4) occasions that you used monensin in medicated cattle feed in combination with chlortetracycline and sulfamethazine, which is not an FDA approved combination for cattle feed.14
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 you comply 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 action, including without limitation, seizure and injunction.
We have the following comments:
1. The FDA Investigators observed that you used the over-the-counter drug amprolium in medicated feed for sheep, which is a “minor species” as defined in the FD&C Act. Amprolium is not FDA approved for use in sheep feed.15 The Investigators also observed that you used the over-the-counter drugs monensin (b)(4) or lasalocid in feed for goats, a minor species. Monensin is approved for use in goat feed at a maximum level of 20g/ton16 and lasalocid is not approved for use in goat feed.17 Therefore, these uses would be an extra-label use of the animal drug in your feed, which is illegal.18 However, under certain circumstances, FDA may decide not to bring enforcement action against this illegal use. We recommend you familiarize yourself with those circumstances, which are described in FDA’s Compliance Policy Guide Sec. 615.115, “Extralabel Use of Medicated Feeds for Minor Species,” available at https://www.fda.gov/media/71960/download. The circumstances FDA considers include, in part: whether the feed is for a minor species, whether there is express prior written recommendation and oversight by a licensed veterinarian, whether the feed is formulated, manufactured, and labeled appropriately, and whether you have prepared and maintained records as required.
2. 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/regulatory-information/search-fda-guidance-documents/cvm-gfi-235-current-good-manufacturing-practice-requirements-food-animals
• Guidance for Industry #245, “Hazard Analysis and Risk-Based Preventive Controls for Food for Animals”
• https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-245-hazard-analysis-and-risk-based-preventive-controls-food-animals
3. For more information about FDA’s current thinking on the requirements of 21 CFR Part 225 and VFDs, see:
• Medicated Feeds | FDA
• https://www.fda.gov/animal-veterinary/animal-food-feeds/medicated-feeds
• Veterinary Feed Directive (VFD) | FDA
• https://www.fda.gov/animal-veterinary/development-approval-process/veterinary-feed-directive-vfd
• Drugs with Veterinary Feed Directive (VFD) Marketing Status | FDA
• https://www.fda.gov/animal-veterinary/development-approval-process/drugs-veterinary-feed-directive-vfd-marketing-status
• CVM GFI #120 Veterinary Feed Directive Regulation Questions and Answers | FDA
• https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-120-veterinary-feed-directive-regulation-questions-and-answers
• Blue Bird Labels | FDA
• https://www.fda.gov/animal-veterinary/medicated-feeds/blue-bird-labels) A VFD authorizes a customer to receive a Type B or Type C medicated feed. If a customer receives a Type B medicated feed, the customer must follow appropriate mixing directions so that the resulting Type C medicated feed conforms to the VFD drug approval and the VFD authorizing the use of the VFD feed. This website has representative labeling with mixing instructions for Type B medicated feeds. If a customer receives a type C medicated feed, the customer must have information such as feeding instructions and warnings in order to use the VFD feed safely. This website includes instructions, “Searching for Blue Bird Labels,” and a link to a database containing FDA approved representative (“Blue Bird”) labeling that feed mills use to prepare adequate labeling for their VFD feeds.
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 timeframe within which you will complete the correction. If you believe you have complied with the FD&C Act and FDA regulations, include your reasoning and any supporting information for our consideration.
Please send your written response to Kevin A. Beavers, Compliance Officer, U.S. Food and Drug Administration, 8050 Marshall Dr., Suite 205, Lenexa, Kansas 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
_____________________
1 See Section 402(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), [21 U.S.C. § 342(a)(4)] and 21 CFR 507.1(a)(1)(ii).
2 See Section 301(uu) of the FD&C Act [21 U.S.C. § 331(uu)].
3 See Section 512(a)(2) of the FD&C Act [21 U.S.C. § 360b(a)(2)].
4 See Section 501(a)(6) of the FD&C Act 21 U.S.C. § 351(a)(6)]and 21 CFR 558.6(c)(2) and 21 CFR 558.6(a)(3).
5 See Section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]; see also section 504(a)(1) of the FD&C Act [21 U.S.C. § 354(a)(1)].
6 See Section 501(a)(2)(B) of the FD&C Act [21 U.S.C. § 351(a)(2)(B)] and 21 CFR 225.1(b)(1).
7 See Section 512(a)(2)(A) of the FD&C Act [21 U.S.C. § 360b(a)(2)(A)].
8 See Section 501(a)(6) of the FD&C Act [21 U.S.C. § 351(a)(6)].
9 See Section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].
10 See 21 CFR 558.140.
11 See also 21 CFR 507.27(b).
12 See 21 CFR 558.355(d)(6).
13 See 21 CFR 558.55, 21 CFR 558.58, and 21 CFR 558.355 for approved uses of amprolium and monensin in animal food.
14 See 21 CFR 558.355 and 21 CFR 558.140 for approved uses of monensin and for chlortetracycline in combination with sulfamethazine, respectively.
15 See 21 CFR 558.55 for approved uses of amprolium.
16 See 21 CFR 558.355(f)(6).
17 See 21 CFR 558.311 for approved uses of lasalocid.
18 See 21 CFR 530.11(b).
No comments:
Post a Comment