- Docket Number:
- Issued by:
Guidance Issuing OfficeCenter for Veterinary MedicineOffice of Regulatory Affairs
The *Center for* Veterinary Medicine has long been aware of the phenomenon of so-called "cross-contamination" of feed with low levels of drugs during manufacture of medicated animal feeds. This carryover may occur as a result of utilizing equipment common to the manufacture of both medicated and non-medicated feed. It may be due to design and construction of the equipment, poor dust control, or inadequate clean-out procedures between sequential batches of feed. From inspectional experience, however, it is apparent that even in the best constructed and managed feed mill the complete elimination of all batch to batch carryover is not a practical possibility given the realities of feed manufacturing. The Current Good Manufacturing Practice Regulations (CGMPRs) recognize this by requiring adequate clean-out procedures so as to "avoid" excessive drug carryover and prevent what is termed "unsafe" contamination.
Where drug carryover from the manufacture of medicated feed results in unsafe contamination in other feeds, it constitutes a violation of the good manufacturing practice regulations (21 CFRa). The feeds are adulterated within the meaning of 501(a)(2)(B) of the Act. The adulteration of non-medicated feed with unsafe contamination is likewise a violation of GMPRs (21 CFRb).
Our interpretation of the CGMPRs is that in each and every instance where the mill clean-out procedures or other manufacturing practices are such that carryover is suspected, it is our burden to prove that the contamination is "unsafe . . .". To do this requires inspectional and analytical information as to the immediate cause and responsibility for the carryover and an analysis by veterinarians and toxicologists not only as to the safety of the carryover residues to the animal for whom the feed is intended but in the case of food-producing animals, whether the meat, milk, or eggs may be expected to contain tissue residues hazardous for humans.
At the present time we are preparing a proposal concerning this problem for publication in the Federal Register. This will announce requirements for data to provide a basis for establishing safe tolerances for drug carryover in animal feed. It will also require submission of methodology sufficient to determine low level carryover residues in animal feed. Completion of the task will require some years.
The document will propose establishing several classes or groups of drugs ranging from, on the one hand, those for which we have data to establish the safety of drug carryover at the lowest established use level to, on the other hand, those which are suspect or known carcinogens or which exhibit special toxicological properties. In between will be other classes of drugs for which a carryover level can be tolerated with the level being set at a point where the data establishes that it will be safe.
Pending promulgation of a regulation defining "unsafe" contamination and setting forth tolerances for drug carryover in a feed as a result of feed mill manufacturing procedures, inspectional effort will be concentrated in the area of drug carryover contamination by those drugs exhibiting carcinogenic or other special toxicological properties. These have been tentatively identified as including:
Carryover of drugs not in the above group may be unsafe if the level of carryover is sufficient: Therefore, good manufacturing practice requires they also be controlled.
In addition to formal regulatory action, withholding and/or withdrawal of approval for new animal drug applications *(FD-1900s)* for medicated feeds will be considered when levels of contamination are
more than "de minimus," and constitute a hazard to animal or human health.
a 21 CFR 225.65
b 21 CFR 225.1(b)
*Material between asterisks is new or revised*
You can submit online or written comments on any guidance at any time (see 21 CFR 10.115(g)(5))
If unable to submit comments online, please mail written comments to:
Food and Drug Administration
5630 Fishers Lane, Rm 1061
Rockville, MD 20852
All written comments should be identified with this document's docket number: FDA-2021-D-0638.