Inspections, Compliance, Enforcement, and Criminal Investigations
Tri State Agri Services, LLC 10/5/12
Department of Health and Human Services
|Public Health Service|
Food and Drug Administration
4040 North Central Expressway
Dallas, Texas 75204-3128
October 5, 2012
Tim Dieckhoff, President
Tri-State Agri Services, LLC
c/o Main Street Feeds, Inc.
109 Main Street
Monett, Missouri 65708
Dear Mr. Dieckhoff:
An inspection of your licensed medicated feed mill, Tri State Agri Services, LLC, located at 101½ North Main Street, Afton, Oklahoma conducted by the Food and Drug Administration (FDA) on February 15, 2012 through March 1, 2012, documented several significant deviations from the Current Good Manufacturing Practice (CGMP) regulations for licensed medicated feed manufacturers, Title 21, Code of Federal Regulations, Part 225 (21 CFR § 225.10 - 225.115). Such deviations cause the medicated feed manufactured at your facility to be adulterated under Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), 21 U.S.C. § 351(a)(2)(B). In addition, your firm manufactured and distributed a medicated feed, Stocker Mineral C-3500 B-2100, which contained an unapproved concentration of lasalocid. Your failure to manufacture and label the medicated feed in conformance with the approval for the drug combination of lasalocid and chlortetracycline contained in the feed caused the medicated feed to be unsafe under section 512(a)(2)(A)(i) of the FD&C Act, 21 U.S.C. § 360b(a)(2)(A)(i), and adulterated under section 501(a)(6), 21 U.S.C. § 351(a)(6). Further, your failure to use lasalocid in conformance with an approved use of the drug caused the drug to be unsafe under section 512(a)(1)(A) of the FD&C Act, 21 U.S.C. § 360b(a)(1)(A), and adulterated under section 501(a)(5) of the FD&C Act, 21 U.S.C. § 351(a)(5). Finally,the medicated feed Stocker Mineral C-3500 B-2100 is misbranded under section 502(f) of the FD&C Act, 21 U.S.C. 352(f), because the product labeling lacks adequate directions for use.
We have reviewed your response dated March 26, 2012 in which you assert you have taken corrective action to address all 14 observations noted in the Form FDA-483 issued to your firm. However, several of the violations noted in the Form FDA-483 are recurring observations that apparently were not corrected following previous inspections of your facility in February 2005 and April 2007. In addition, you did not submit any supporting documentation, such as updated written procedures, to demonstrate that you have in fact implemented corrective action following this most recent inspection.
Medicated Feed CGMP deviations observed during the inspection include, but are not limited to, the following:
1. For feeds requiring a medicated feed mill license for their manufacture and marketing, at least three representative samples of medicated feed containing each drug or drug combination used in the establishment shall be collected and assayed by approved official methods, at periodic intervals during the calendar year [21 CFR 225.58(b)(1)]. Our inspection found that your firm failed to perform all of the required assays during 2011. For example:
Your firm manufactured thirteen lots of medicated feeds containing (b)(4), with active ingredient amprolium, during 2011. However, only one of the three required assays was conducted, and as discussed below, the result of this single analysis was below the minimum assay limit and considered “out-of-limits”.
Further, your firm manufactured five lots of medicated feed containing (b)(4), with active ingredient carbadox during 2011 and your firm did not conduct any of the required assays.
This is a recurring observation from the April 2007 and February 2005 inspections of your firm.
2. Where the results of assays indicate that the medicated feed is not in accord with label specifications or is not within permissible assay limits, you are required to investigate and implement corrective action. Additionally, an original or copy of the record of such action needs to be maintained on the premises [21 CFR 225.58(d)]. Our inspection found that your firm failed to investigate and implement corrective action when your assay results showed medicated feeds not within permissible assay limits. For example:
Your firm manufactured and distributed Pullet Starter Complete (lot E10X11) labeled with a concentration of 0.013% of amprolium. Your 2011 assay for amprolium (lot E10X11) was 0.0095%, or 73% of formulation. This result was outside the permissible assay range of 80–120% of the formulated level and is considered out of limits [See 21 CFR 558.4]. Your firm failed to recognize that the result was below the minimum permissible assay limit, did not conduct an investigation into the cause of the out-of-limits assay and did not implement corrective actions.
This is a recurring observation from the February 2005 inspection of your firm.
3. All equipment that comes in contact with active drug components, feeds in process, and finished medicated feed is subject to all reasonable and effective procedures to prevent unsafe contamination of manufactured feed. The steps used to prevent unsafe contamination of feeds shall include physical means (vacuuming, sweeping, or washing), flushing, and/or sequential production of feeds [21 CFR 225.65(b)]. Our inspection shows your firm failed to take adequate steps to prevent unsafe contamination of feed as you failed to follow your own written procedures for flushing, sequencing, and cleaning of equipment to prevent the cross-contamination of finished feeds. For example:
Your mixing procedure requires a flush of the mixing equipment between production of feed containing (b)(4) (which contains (b)(4)) and the production of dairy, layer, broiler or any finisher feed. A review of your production records showed your firm manufactured Beef Crumbles AS-700 2+2 (lot K167X11) containing (b)(4), and did not conduct a flush or physical cleanout of the mixer and other equipment following production of this lot. Subsequently, this equipment was used to manufacture MFM 16% Layer Crumbles lot K168X11, which was labeled for feeding poultry layers. (b)(4) is not approved by FDA for use in feed for laying hens.
Further, your mixing procedure requires a flush of the equipment between production of feed with (b)(4)(which contains (b)(4)) and the production of dairy, layer or any finisher feed. A review of your production records showed your firm manufactured Prep 19 (lot K217X11) containing (b)(4), and did not conduct a flush or physical cleanout of the mixer and other equipment following the production of this lot. Subsequently, this equipment was used to manufacture 20% Protein Salt Mix lot K218X11, which was labeled for feeding beef cattle on pasture. (b)(4) is not approved by FDA for use in feed for cattle.
4. Your master record file must include the name and weight percentage or measure of each drug and nondrug ingredient to be used in manufacturing a stated weight of a medicated feed [21 CFR 225.102(b)(1)(ii)]. In addition, your production records must include the quantity and name of drug components used in each batch or run of medicated feed produced [225.102(b)(2)(ii)]. Our inspection found that in your production of multiple lots of two medicated feeds, you failed to follow the formula contained in the master record file and included in the production records. Therefore, your master record file failed to accurately reflect the name and weight percentage or measure of each drug ingredient used and your production records failed to reflect the accurate quantity and name of drug components used. For example:
The formula in your master record file, which is also the formula contained in your production records, indicate that (b)(4) will be used to make Pullet Starter Complete and MFM 18% Chick Starter Grower. However, your firm used (b)(4) instead of (b)(4) in the production of the following medicated feeds:
Nine lots of Pullet Starter Complete were produced between March 1, 2011 and November 21, 2011 using (b)(4), in place of (b)(4).
Four lots of MFM 18% Chick Starter Grower were produced between October 4, 2011 and November 19, 2011 using (b)(4), in place of (b)(4).
5. Batch production records shall be checked by a responsible individual at the end of the working day in which the product was manufactured to determine whether all required production steps have been performed. If significant discrepancies are noted, an investigation shall be instituted immediately, and the production record shall describe the corrective action taken [21 CFR 225.102(b)(4)]. Although the production records we reviewed for ten batches of medicated feed produced between 5/1/11 and 2/14/12 documented the significant discrepancies listed below, you failed to describe any corrective action taken on the production records. For example:
Beef Crumbles AS-700 2+2 lot K167X11 was not properly sequenced at the mixer and pellet mill and was not followed by a flush as required by your mixing procedure. However, we found no evidence indicating that this error was investigated or that corrective action was taken.
(b)(4) pounds of Pullet Starter Complete lot E10X11 was bagged, although the production record indicated that only (b)(4) pounds of feed had been manufactured. However, we found no evidence indicating that this error was investigated or that corrective action was taken.
This is a recurring observation from the February 2005 inspection of your firm.
6. A master record file shall be prepared, checked, dated, and signed or initialed by a qualified person and shall be retained for not less than 1 year after production of the last batch or production run of medicated feed to which it pertains [21 CFR 225.102(b)(1)]. Our inspection shows a number of your master record files are not dated and signed and/or retained for at least one year after production of the last batch or production run of medicated feed. For example:
The Stocker Mineral C-3500 B-2100 formulation included an unapproved concentration of (b)(4). This master record file was not signed and dated, indicating the file had not been reviewed by a qualified person.
The label for Stocker Mineral C-3500 B-2100 was revised on or after December 5, 2011. The master record file lacked the previous version of the label that had been used for eighteen lots produced prior to the label revision. The previous label must be retained for at least one year after production of the last batch or production run of that medicated feed.
The Master Record File Stored Formula Report for Pullet Starter Complete Medicated had a revision date of November 11, 2011. However, the file did not include the previous version and there was no documentation of what changes occurred. The previous label must be retained for at least one year after production of the last batch or production run of that medicated feed.
7. Medicated feed manufacturers must maintain a file containing a record of each oral or written complaint relating to the safety and effectiveness of a medicated feed. The record must include the date of the complaint, complainant’s name and address, name and lot or control number or date of manufacture of the medicated feed involved, and specific details of the complaint. This record must also include all correspondence from the complainant and/or memoranda of conversations with the complainant, and a description of all investigations made by the manufacturer, as well as the method of disposition of the complaint [21 CFR 225.115(b)(1)]. Our inspection shows your complaint records are incomplete. For example:
Your firm received a complaint regarding Stocker Mineral C-3500 B-2100. Although you accepted two lots of feed returned by the complainant, investigated the source of the formulation and made preliminary changes to the labeling, you failed to maintain any record documenting the complaint, including the correspondence from the complainant and/or memoranda of conversations, and a description of all related investigations.
In addition to the above CGMP deviations, you adulterated the medicated feed Stocker Mineral C-3500 B-2100 (for beef cattle on pasture) by failing to manufacture and label it in conformance with an approved use of the drug combination of lasalocid and chlortetracycline contained in the feed. You also adulterated the Type A medicated article lasalocid by failing to use it in conformance with an approved use of the drug. Our investigator determined that since April 2008 your firm has manufactured and distributed eighteen lots of Stocker Mineral C-3500 B-2100 containing an unapproved concentration of lasalocid. The labeled amount of lasalocid in this feed (2138.5 g/ton) exceeds the maximum approved level for the drug in Type C feed (30 to 600 g/ton), as specified in 21 CFR 558.311(e)(1)(xxviii). As such, this medicated feed is deemed unsafe under section 512(a)(2)(A)(i) [21 U.S.C. 360b(a)(2)(A)(i)] of the FD&C Act and adulterated under 501(a)(6) [21 U.S.C. 351(a)(6)] of the FD&C Act. In addition, your failure to use lasalocid in conformance with an approved use of the drug caused the drug to be unsafe under section 512(a)(1)(A) of the FD&C Act, 21 U.S.C. § 360b(a)(1)(A), and adulterated under section 501(a)(5), 21 U.S.C. § 351(a)(5).
Finally,the medicated feed Stocker Mineral C-3500 B-2100 is misbranded because feeding the product as directed in the “Directions for Use” section of the label would provide a sub-potent level of chlortetracycline to the animal. Because the feeding instructions have been adjusted to account for the elevated amount of lasalocid in the product, the chlortetracycline concentration when fed as directed on the label falls below the approved levels specified in 21 CFR 558.311(e)(1)(xxviii). For example, feeding 0.056 pounds/head/day of the finished product will provide an animal 60 mg/head/day of lasalocid and 98 mg/head/day of chlortetracycline. 21 CFR 558.311(3)(1)(xxviii) requires 10 mg per pound of body weight of chlortetracycline per day, so when fed at this level this product contains only enough chlortetracycline to dose a 9.8 pound calf. At the upper end of your feeding range (0.281 pounds/head/day) the product contains only enough chlortetracycline to dose a 49 pound calf. Accordingly, the product is misbranded under section 502(f) of the FD&C Act, 21 U.S.C. 352(f) as its label lacks adequate directions for use.
The above is not intended as an all-inclusive list of deficiencies of your facility. As a licensed manufacturer of medicated feeds, you are responsible for assuring your overall operation and the products you manufacture and distribute are in compliance with the Act and its implementing regulations.
You should take prompt action to correct the noted violations and establish procedures whereby such violations do not recur. Failure to promptly correct these violations may result in regulatory and/or administrative sanctions. These sanctions include, but are not limited to, seizure, injunction and/or notice of opportunity for a hearing on a proposal to withdraw approval of your Medicated Feed Mill License under section 512(m)(4)(B)(ii) [21 U.S.C. 360b(m)(4)(B)(ii)] of the Act, and 21 CFR 515.22(c)(2). Based on the results of the inspection, evaluated together with the evidence before FDA when the Medicated Feed License was approved, the methods used in, or the facilities and controls used for, the manufacture, processing, and packing of medicated feeds are inadequate to assure and preserve the identity, strength, quality, and purity of the new animal drug therein. This letter constitutes official notification under the law and provides you an opportunity to correct the deficiencies in your operations.
At FDA’s next inspection of your facility, we will confirm that you have taken the corrective action that you asserted you have taken in your response dated March 26, 2012, and that the above CGMP violations do not recur. You should notify this office, in writing, within fifteen (15) working days of receipt of this letter of any additional steps you have taken to bring your firm into compliance with the law. Your response should include an explanation of each additional step being taken to correct the violations discussed in this letter, and prevent their recurrence. If corrective actions cannot be completed in fifteen (15) working days, state the reason for the delay and the date by which the corrections will be completed. Include copies of any available documentation demonstrating that corrections have been made.
Your firm’s response should be sent to the Food and Drug Administration, 4040 North Central Expressway, Suite 300, Dallas, Texas 75204, Attention: Rose M. Ashley, Compliance Officer. Refer to the unique identification number, 2012-DAL-WL-002, when replying. If you have any questions about the content of this letter please contact: Rose M. Ashley at (210) 308-1407.
Reynaldo R. Rodriguez, Jr.