Animals originating

Vital Safety Evaluation of Biotechnology Products Derived from CeU Liaes of Human or Animal Origin," ICH Harmonized Tripartite Guideline,... 

Human Extended Insulin Zinc Suspension. Ultralente Humulin U is a long-acting form of human insulin produced by recombinant DNA techniques. It is adrninistered subcutaneously and should not be given intravenously. The time course of this preparation is similar for onset of activity but shorter for maximum activity and duration of action compared with ultralente preparations of animal origin. Insulins of the lente series can be mixed in any proportion to obtain the desired dose and modified activity. 

EEC Directive on pesticide residues m foodstuffs of animal origin... 

Resins can be divided into natural and synthetic types. Natural resins have a vegetable or animal origin. Typical examples are rosins. Synthetic resins result from controlled chemical reactions, and can be divided into two subgroups. 

The pharmaceutical industry has employed materials of plant and animal origin as sources of drugs. The industry has utilized the life processes of either plants or animals and microorganisms to produce medicinal and antibiotic products. 

Biotin can be synthesized by the human colon flora. The question to which extent this production contributes to covering the host-organism s requirements is, however, subject to discussion. In most foods of animal origin as well as in cereals, biotin prevails in the protein (= enzyme)-bound form as e-N-biotinyl-L-lysine (= biocytin). Brewer s yeast, liver, soya beans, and peanuts number among the biotin rich foods [1]. 

Most foods of animal origin contain nicotinamide in the coenzyme form (high bioavialability). Liver and meat are particularly rich in highly bioavailable niacin. Most of the niacin in plants, however, occurs as nicotinic acid in overall lower concentrations and with a lower bioavailability. The major portion of niacin in cereals is found in the outer layer and its bioavailability is as low as 30% because it is bound to protein (niacytin). If the diet contains a surplus of L-tryptophan (Ttp), e.g., more than is necessary for protein synthesis, the liver can synthesize NAD from Trp. Niacin requirements are therefore declared as niacin equivalents (1 NE = 1 mg niacin = 60 mg Trp). 

Milk, milk products, and foods of animal origin contain high amounts of (free) riboflavin with good bioavailability. In foods of plant origin, the majority of riboflavin is protein-bound and therefore less bioavail-able. Cereal germs and bran are plant sources rich in riboflavin [1]. 

As investigations with polysaccharides of microbiological, plant, and animal origin revealed the presence in these substances of uronic acids, it became necessary to know more about the acids. Moreover, the occurrence of uronic acids in plant gums and pectic substances, and the structures of urinary... 

EC Introduces detailed specifications as regards the requirements laid down in Coundl Directive 93/42/EEC with respect to medical devices manufactured utilizing tissues of animal origin... 

Council Regulation (EEC) No. 2377/90 of 26 June 1990 laying down a Commrmity procedure for the establishment of maximum residue limits for veterinary medicinal products in foodstuffs of animal origin. 

The Community procedure for establishing MRLs of veterinary medicines in foodstuffs of animal origin is set down in Council Regulation (EEC) No. 2377/90 as amended by Council Regulation (EC) No. 1308/1999. The regulations are supported by detailed guidance contained in The Rules Governing Medicinal Products in the European Union, Volume 8 - Maximum Residue Limits. 

A statement indicating whether or not the device is manufactured utilising tissues of animal origin as referred to in Directive 2003/32/EC and the risk management measures in this connection which have been applied to reduce the risk of infection... 

VITAMIN Bi2 IS FOUND ONLY IN FOODS OF ANIMAL ORIGIN... 

Fatty acids of plant, animal, and microbial origin usually consist of an even number of carbon atoms in the straight chain. The number of carbon atoms of fatty adds in animals may vary from 2 to 36, whereas some microorganisms may contain 80 or more carbon atoms. Also, fatty adds of animal origin may have one to six ds double bonds, whereas those of higher plants rarely have more than three double bonds. Fatty adds also may be saturated, monounsaturated (monoenoic), or polyunsaturated (polyenoic) in nature. Some fatty acids may consist of branched chains, or they may have an oxygenated or cyclic structure. 

In this section, the general requirements laid down in Directive 96/46/EC and in the guidance document SANCO/825/00 are discussed. Furthermore, specific requirements for the different matrices (food of plant and animal origin, soil, water, air, and body fluids and tissues) will be illustrated. 

Owing to the complexity of multi-residue methods for products of animal origin, it is not possible to outline a simple scheme however, readers should refer to methods described in two references for detailed guidance (Analytical Methods for Pesticides in Foodstuffs, Dutch method collection and European Norm EN 1528. ) There is no multi-method specifically designed for body fluids and tissues. The latter matrix can be partly covered by methods for products of animal origin. However, an approach published by Frenzel et al may be helpful (method principle whole blood is hemolyzed and then deproteinized. After extraction of the supernatant, the a.i. is determined by GC/MS. The LOQ is in the range 30-200 ag depending on the a.i.). 

Specific requirements 4.2.1 Food of plant and animal origin... 

Validation of the analytical methods for food of animal origin has to be performed with milk, egg, meat, and fat. The latter is required only if log Pqav is >3 and metabolism studies indicate significant residues in fat, because in this case it is likely that an MRL will be set. Other tissues such as kidney or liver must be validated only if an MRL is set or proposed for these tissues. The issue of the general necessity of analytical methods for food of animal origin is not addressed in Directive 96/46/EC or SANCO/825/00. At this moment, the Working Group Pesticide Residues proposes an MRL on a case-by-case basis. However, a pragmatic approach is presented in SANCO/825/00. 

According to Directive 96/68/EC, an analytical method for the determination of residues in food of animal origin is not required when metabolism study in animals is not required. On the other hand, according to Point 6.4 of the Directive, where a feeding study is required, an analytical method for the determination of residues in products of animal origin must be submitted. In other cases, the requirement for an analytical method depends on the establishment of an MRL for food commodities of animal origin. 

The second requirement is that enforcement methods for food must be validated by an independent laboratory [independent laboratory validation (ILV)]. The sample set is identical with the general sample set (see Section 4.1). If the method is identical for all four crop groups (mentioned at the beginning of the section), it may be sufficient to perform the ILV for plant materials with a minimum of two matrices, one of them with a high water content. In the case of food of animal origin, the ILV should be performed with at least two of the matrices milk, egg, meat, and, if appropriate, fat. 

Analytical methods for the determination of residues in body fluids and tissues must be submitted only if the a.i. is classified as toxic or highly toxic. The method has to be validated only at the LOQ in general blood 0.05 mgL and tissues 0.1 mgkg (meat or liver, if not investigated under food of animal origin, see Section 4.2.1). 

In the case of products of animal origin, validation should be performed, where appropriate, with milk, liver, kidney, muscle, fat, and egg. 

---