3. Category II, Group B drugs

Types C and D medicated

feed articles manufactured from Type C articles containing

up to 40X the highest continuous use level.

The term "highest continuous use level" means the highest dosage at which the drug is approved for continuous use through the feeding period or, if not approved for continuous feeding, it means the highest level for disease prevention or control fed continuously for the duration of disease susceptibility. If the drug is approved for

multiple species at different use levels, the highest level

would govern under this definition.

Category II, Group C drugs would be subject to Section 512 in all medicated feed levels because of their special toxicological

problems.

See Table 1. Refer to Tab J for a tabular listing of existing drugs under this concept.

*80X and 40X means 80 and 40 times the highest continuous medicated feed use level of the drug specified in 21 CFR Part 558. The 80X and 40X drug levels in categories IIA and IIB medicated feed articles are the dividing lines between medicated feed articles requiring FD-1800 approval and not requiring FD-1800 approval. The manufacture of medicated feed articles from Type C articles containing drug levels at 80X or 40X and below do not require FD-1800 approval. Approval is required when manufactured from sources with drug levels above 80X and 40X for drugs in categories IIA and IIB, respectively.

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The significance of potential residues varies according to the toxicological significance (including carcinogenicity), or the lack of data upon which to make a complete toxicological evaluation. Therefore, the categorization in the Drug Carryover document is an appropriate basis for the graded classification of drugs in feeds not deemed as new animal drugs. This rational is amplified in the following text.

Since a Type A animal feed is a new animal drug (unless there is a determination of general recognition that it is safe and effective), everyone receiving the Type A product for

manufacturing purposes should hold an FD-1800 under the

provisions of Section 512(a)(1). Thus it would be necessary for the manufacturer of a Type B, C, or D medicated feed from a Type A premix to hold an FD-1800. However, there is no requirement

that subsequent use of the Type B, whether in another Type B or Types C or D animal feeds, must be subject to Section 512 of the Act in that diluted form. In this way, some animal feeds of

Types B, C, and D may be legally considered not subject to Section 512(m) when made from a Type B or more dilute medicated

feed article.

Category I drugs would be deemed not subject to Section 512 in Type B, C, and D medicated feeds made from an approved Type B medicated feed article.

Actually even Type B feeds made from a Type A premix should not require 1800's because of the considerable human safety of these drugs in feed use, but that is not possible because Section 512(a) (1) requires the recipient of a new animal drug (which, by definition, is every new animal drug Type A premix) to hold an approved FD-1800. Footnote 1/

Category II, Group A drugs would not be subject to Section 512 to make Type D feeds and Type C feeds containing up to 80X the highest continuous use level. These drugs, too, have a high degree of human safety

almost as great as Category I drugs.

Footnote 1/: Removing Category I drugs from Section 512(m) in Type C articles would require revision of the medicated feed definitions proposal by deleting the statement, "[w]hen a Type C article is fed undiluted or offered free-choice, in amounts to not less than one-half pound per head per day, the article shall not produce residues in food from food-producing animals that are unsafe within the meaning of Section 512 of the Act." (43 FR 2533, January 17, 1978, Section 558.3(b)(3)) This concept, which has its genesis in a belief that Type C feeds (supplements under Part 558.3) were likely to be misused by direct feeding to animals without appropriate dilution, is no longer appropriate, for a number of reasons which result in self-limiting use of the article: (1) It is reasonable to assume that adequate directions for use will be followed. This is a basic concept even in the availability of OTC drugs for human self-medication. The Bureau has no record or indication of deliberate or inadvertent misuse of feeding such products directly. (2) Even if isolated use errors occur, other human safety factors come into play. The animals will ordinarily refuse consumption, go off feed, or become ill (unless specifically formulated for self-feeding) so such error would be corrected quickly. The high levels of vitamins and minerals commonly formulated into these articles as well as elevated drug levels cause these articles to be unpalatable. (3) Economic factors make the user well aware that the product is not intended for direct feeding. (4) Visual, textural, and olfactory characteristics usually identify the article to the user as not intended for direct feeding.

Therefore, the Type C feeds should be available at high concentrations without further control under the 512(m) approval process. The 80X level affords a high degree of flexibility yet offers some degree of restriction in recognition of a lower order of toxicological categorization in the Drug Carryover document.

The same rationale applies to the maxiumum 40X Type C level for Category II, Group B drugs. As the degree of toxicological concern rises, the need for increased control rises. Thus, Category II, Group C drugs in feed should require preapproval control at all drug levels in feeds because they are carcinogens.

Under existing practices, many Type D feeds require an approved FD-1800. Thus, expense and "red tape" are an inherent part of the process. Being faced with those factors, applicants at all levels, even mixer-feeders, usually opt for the most economical source of the drug, i.e., the premix, whether or not their operation is sophisticated enough to handle and control such an article adequately. However, if given the option to purchase a significantly diluted form of the drug, i.e., 40X and 80X, which could contain added vitamins and minerals, without holding an FD-1800, users would be expected to opt for this kind of article to avoid the "red tape" and delays of an application approval.