Date: September 30, 2009
From: Director, Office of Surveillance and Compliance (HFV-200)
Subject: Nationwide Survey of Distillers Grains for Antibiotic Residues
To: All FDA District Directors, FDA Regional and District Laboratory Directors, FDA District Investigations Branch Directors, Regional Food and Drug Administration Directors and FDA District Compliance Branch Directors
ORA Concurrence #2009021101
FACTS Assignment # 1100391
To determine the extent and level of antibiotic residues in a limited number of domestic and import samples of distillers grains. Since this assignment is primarily intended to generate data for policy development, it is not expected to result in regulatory action.
FDA’s CVM is concerned about potential animal and human health hazards from the use of distillers products, hereafter referred to as distillers grains, as an animal feed ingredient due to the possibility of antibiotic residues. Distillers grains results from the fermentation of various crops, such as corn, to produce ethanol.
In North America, approximately 98% of the distillers grains on the market are a by-product from the fuel ethanol industry, while the remaining 1 to 2% are a by-product from the beverage ethanol industry. Approximately 3.2 to 3.5 million metric tons of distillers grains are produced annually in North America with about 2.65 million metric tons available for domestic use in the U.S. and Canada. Of these 2.65 million metric tons, approximately 90% is used in animal feed with currently over 80% used in ruminant diets. Distillers grains are also finding their way into poultry, swine, equine and fish feed. However, because of the increased demand for fuel ethanol, the production of distillers grains is expected to increase in the next couple of years further increasing the quantity of distillers grains available for all types of animal feed.
Bacterial contamination of the fermenter is an ongoing problem for commercial fuel ethanol production facilities. Both chronic and acute contamination is of concern since bacteria compete with the ethanol-producing yeast for sugar substrates and micronutrients. Lactic acid levels often rise during bouts of contamination, suggesting that the most common contaminants are lactic acid producing bacteria. Currently, antibiotics such as virginiamycin (VIR), penicillin (PEN) and erythromycin, etc. are believed to be used in the U.S. as antimicrobials during the fermentation process to control bacterial contamination. CVM is concerned because the available literature has shown that not all antibiotics are markedly degraded or metabolized to inactive compounds during ethanol production. In fact, some antibiotics may be concentrated in the distillers grains where they may be present at levels as high as three times the level added to the fermenter on a dry weight basis.
Currently, we have limited data on the extent and levels of antibiotics in distillers grains that are produced by either domestic or foreign ethanol facilities and marketed as animal feed ingredients in the U.S. Because of this limited data and because of the marked increase in the amount of distillers grains used in animal feed, CVM believes it is important for the agency to conduct a limited survey to determine the extent and levels of antibiotic residues in distillers grains produced at U.S. and foreign ethanol production facilities.
In December of 2008, the Division of Planning, Evaluation and Management established a new PAC code for antibiotic residues in non-medicated animal feeds -- PAC code 71003K - Feed Contaminants Program - Antibiotics. The PAF that will be used with this new PAC is ANT - Antibiotics in Foods and Feeds. This PAC will be used for both import and domestic products and will be associated with compliance program 7371.003 - Feed Contaminants.
(Please note: Workplan resources (FTEs) for this assignment will come from PAC code 71003A – Pesticides/Industrial Chemicals; however, the work (sample collection and analysis for antibiotic residues and moisture content) should be reported under PAC 71003K -- Feed Contaminants Program (Antibiotics).)
1. Overview of Samples to Collect
Resources have been allocated under the fiscal year (FY) 2010 workplan to collect 60 distillers grains samples (40 domestic and 20 import) under PAC code 71003A – Pesticides/Industrial Chemicals. The 60 distillers grains samples to be collected during this assignment are divided among 13 FDA district offices as described in Attachment 1. These 60 distillers grains samples will be collected as investigational samples and sent to the following servicing labs: NRL, SRL, ARL, DEN-LAB, PRL-SW and PRL-NW.
For the purposes of this assignment, distillers grains are feed ingredients that meet the Association of American Feed Control Officials Incorporated (AAFCO) definitions for Distillers Dried Grains (DDG), Distillers Wet Grains (DWG), Distillers Dried Grains with Solubles (DDGS), Distillers Dried Solubles (DDS), and Condensed Distillers Solubles (CDS) and are offered for sale or for use in animal feed. The definitions for these AAFCO feed ingredients are found on pages 276 and 277 of the AAFCO 2008 Official Publication. If you do not have, or cannot locate, a copy of the AAFCO 2008 Official Publication, please contact Dr. Linda Benjamin at CVM, Division of Animal Feeds (DAF) for assistance in obtaining copies of these definitions (phone: 240-453-6855; e-mail: email@example.com). If Dr. Benjamin is not available, please contact Ms. Carla Tuite at CVM-DAF for assistance (phone: 240-276-9768; e-mail: firstname.lastname@example.org).
DOMESTIC SAMPLES: There are currently more than 200 ethanol biorefineries in the U.S. Most of the domestic ethanol production facilities are located in districts covered by the FDA Central and Southwest Regional Offices. The distillers grains should be collected at the fuel ethanol production facilities or where they are o ffered for sale or for use in animal feeds. CVM does not anticipate that districts will have any problems in locating domestic fuel ethanol production facilities that produce distillers grains for interstate sale as feed ingredients (see Attachment 2). As needed, samples may be collected from the same biorefinery at different locations. (Note: Shaded area in Attachment 2 identified ethanol plants sampled in 2008. Where possible, please collect sample from ethanol plant not already sampled.)
IMPORT SAMPLES: There are at least 16-ports where distillers grains enter into the U.S. These ports are located in districts covered by the FDA Northeast, Central and Pacific Regional Offices. The distillers grains should be collected if they are offered for sale or for use in animal feeds. Imported samples may be identified under the following product codes: 71F-02, 71F-99, 71G-99, and 71Y-99. CVM does not anticipate that districts will have any problems in collecting import samples of distillers grains.
Districts that have difficulty locating domestic fuel ethanol production facilities or identifying imported distillers grains samples should contact Dr. Linda Benjamin at CVM-DAF for assistance (phone: 240-453-6855; e-mail: email@example.com). If Dr. Benjamin is not available, please contact Ms. Carla Tuite at CVM-DAF for assistance (phone: 240-276-9768; e-mail: firstname.lastname@example.org).
2. Sample Identification
For sample identification of the distiller grains investigational samples refer to Chapter 4 of the FDA Investigations Operations Manual (IOM). In addition, please include the name of the state (New Jersey, Maryland, etc) in which the sample was collected.
For FACTS identification of the distiller grains investigational samples, please make sure the collection report is associated with the FACTS Assignment ## xxxxx. This will facilitate tracking of samples in the FACTS database. Please do not create an ad hoc assignment for collection of these samples.
DOMESTIC SAMPLES: Additional information to be recorded on the Collection Report includes the name of the biorefinery, and as thorough a description of the sample as possible. The description of the sample should include 1) the date of manufacturer, 2) the type of distiller grains product collected (DDG, DDGS, DWG, DDS, CDS, etc.), 3) the source material for the fermentation (corn, sorghum, wheat, etc.) and 4) from where the sample was taken (on-line, holding tank, etc). If known, the investigator should identify the antibiotic/antimicrobial agent(s) used by the firm, the level(s) added and where the antibiotic/antimicrobial agent(s) was added during the manufacturing process (yeast propagation tank, fermenter, etc).
IMPORT SAMPLES: Additional information to be recorded on the Collection Report includes the name of the port of entry, origin of sample (country, facility, etc.) and as thorough a description of the sample as possible. If possible, the description of the sample should include 1) the date of manufacturer, 2) the type of distillers grains product collected (DDG, DDGS, DWG, DDS, CDS, etc.), and 3) the source material for the fermentation (corn, sorghum, wheat, etc.). If known, the investigator should identify the antibiotic/antimicrobial agent(s) used by the firm, the level(s) added and where the antibiotic/antimicrobial agent(s) was added during the manufacturing process (yeast propagation tank, fermenter, etc).
3. Collection, Handling and Shipment of Investigational Samples
For collection of the distillers grains investigational samples refer to IOM Chapter 4. Please note that special handling containers are not necessary for the wet distiller grain samples (WDG) and/or wet distiller grain with solubles samples (WDGS); however, in order to maintain their integrity these samples require refrigeration. As referenced in IOM 4.1.7, investigational samples do not need to be collected from lots in interstate commerce or under federal jurisdiction. Collect 10 sub-samples of the distillers grains, each weighing ~454 grams (1 lb), as shown in IOM Chapter 4, Sample Schedule Chart 6 for corn-shelled, meal flour or grits. There is no need to collect 702(b) portions for these investigational samples. If a regulatory follow-up is deemed necessary, then official samples will be collected and the official samples would include a 702(b) portion.
For handling and shipment of the distillers grains investigational samples refer to IOM Chapter 4. As stated above, high moisture samples such as Wet Distiller Grains samples (WDG) and Wet Distiller Grain with Solubles (WDGS) will require refrigeration immediately following collection. Distillers Dried Grains (DDG), Distillers Dried Grains with Solubles (DDGS), Distillers Dried Solubles (DDS), and Condensed Distillers Solubles (CDS) samples collected under this assignment will not require refrigeration. Samples should be sent by overnight mail to your FDA servicing laboratory. Time spent collecting and shipping these samples should be reported under PAC 71003K – Feed Contaminants Program (Antibiotics).
Refer to the Feed Contaminants Compliance Program (http://www.fda.gov/downloads/ AnimalVeterinary/GuidanceComplianceEnforcement/ComplianceEnforcement/ucm113409.pdf) and the FDA IOM for more detailed information about sample collection, sample handling and shipment. As needed, investigators should refer to the IOM, or contact Dr. Benjamin or Ms. Tuite, for guidance on handling and shipment.
4. Sample Analysis
The servicing laboratories are requested to analyze distiller grains samples for antibiotic residues using LIB 4438 “Analysis of Antibiotic in Distillers Grains Using Liquid Chromatography and Ion Trap Tandem Mass Spectrometry.” The servicing laboratory should perform the analysis for antibiotic on a composite of the subsamples collected. As appropriate, the servicing laboratory has the flexibility to combine standards.
As the 2008 survey only detected virginiamycin, erythromycin and tylosin residues, the servicing laboratories have the flexibility to limit their quality control standards to virginiamycin, erythromycin and tylosin. However, if the laboratory identifies an antimicrobial residue other than these 3 standards, quantification must be done with the appropriate standard.
There could be a wide range of moisture content in the distillers grains samples depending on whether they have been dried and the drying process used. Thus, the moisture content should be determined for each sample collected as part of this survey. The moisture content of distillers grains should be determined by AOAC Official Method 934.01, Loss on Drying (Moisture) at 95-100°C for Feeds (Official Methods of Analysis of AOAC International, 17th edition, 2000, volume 1, 4.1.03).
Time spent analyzing these samples for antibiotic residues and moisture content should be reported under PAC 71003K – Feed Contaminants Program (Antibiotics).
FDA labs are encouraged, but are not required, to analyze the distillers grains for mycotoxins (aflatoxins, fumonisins, vomitoxins, zearalenone and/or ochratoxin A) and elements (especially sulfur). Time spent analyzing these samples for mycotoxins and/or elements should be reported under PAC 71003C – Feed Contaminants Program (Mycotoxins) or PAC 71003B – Feed Contaminants Program (Elements).
All analytical results from these samples, including analyses for antibiotic residue, moisture content, mycotoxins and elements should be reported in FACTS.
5. Primary Contact
The primary contact for this assignment is Dr. Linda Benjamin.
If you have any questions about sample collection, sample handling and shipment, please contact her at email@example.com or 240-453-6855. If Dr. Benjamin is not available, please contact either Dr. Randall Lovell at firstname.lastname@example.org or 240-453-6857 or Ms. Carla Tuite at email@example.com or 240-276-9768.
If you have any questions about sample analysis, please contact Dr. Lawrence (Larry) D’Hoostelaere at Lawrence.firstname.lastname@example.org or 301-827-1032 or Dr. Hema de Alwis at Hemakanthi.email@example.com.
REGULATORY/ ADMINISTRATIVE FOLLOW-UP
The Center is currently developing a policy for antibiotic residues in distillers grains. As the primary objective of the assignment is to collect data on antibiotic residues in distillers grains to support policy development, the Center does not anticipate regulatory follow-up. However, if needed, CVM would support administrative and/or regulatory actions (including, but not limited to, untitled letters, warning letters, recalls, seizures and injunctions) when residue levels in distillers grains that are intended for use in animal feeds and are in, or are likely to enter, interstate commerce exceed previously approved levels in Part 558 of Title 21 of the Code of Federal Regulations.
This assignment has a routine priority and the concurrence of ORA. The assignment is directly associated with the Feed Contaminants Program and resources have previously been allocated to it under the FY 2009 Work Plan. The ORA concurrence # is 2009021101. Time spent collecting and analyzing these samples should be reported under PAC 71003K – Feed Contaminants Program (Antibiotics). The anticipated sample collection time for each sample is about 4.2 hours/op for domestic samples and 2.5 hours/op for import samples.
Please refer to FACTS assignment # 1100391 when referring to this assignment.
Daniel G. McChesney, Ph.D.
Director, Office of Surveillance & Compliance
 University of Minnesota, Distillers Grains By-products in Livestock and Poultry Feeds, 2007