animals being treated daily for 7 days with an antibiotic and, from official sales
data, an estimate that 11.92% of these animals were administered injectable for-
mulations. The study concluded that the maximum likelihood of a European
consumer ingesting an injection site, or part of an injection site, was 4 days
annually. Over the same period, 37% of European consumers would not ingest an
injection site.
The sampling of injection site tissues is conducted in accordance with protocols
described in regulatory guidelines (US FDA CVM 1994 ; EMEA-CVMP 2005 ).
When conducting trials on multiple dosing regimens, injections are alternated
between the left and right sides of animals; the last injection site is then sampled
for residue analysis. In all jurisdictions, cylindrical samples weighing approxi-
mately 0.5 kg and measuring 10 cm in diameter and 6 cm in depth for intramuscular
injections, and measuring 15 cm in diameter and 2.5 cm in depth for subcutaneous
injections, are collected. A second concentric ring-shaped sample of approximately
0.3 kg collected from the region immediately surrounding the excised core sample
is required by regulatory agencies in the EU only. All samples are homogenised
thoroughly prior to sub-sampling for residue analysis.
2.2 Risk Management
2.2.1 Residues of Veterinary Drugs and Food Safety
The withdrawal period (also referred to as withdrawal time or withholding period)
is the interval between the time of the last administration of a veterinary drug and
the time when the animal can be safely slaughtered for food, or milk or eggs can be
safely consumed. Compliance with the withdrawal period provides a high degree of
assurance to both producers and consumers that the concentration of residues in
foods derived from treated animals will not exceed the MRL. Withdrawal periods
are typically assigned on the basis of results of a residue depletion study using
non-radiolabelled drug in which the veterinary drug product proposed for mar-
keting is administered at the highest label rate, the shortest dosing interval and
for the longest duration. These conditions represent a worst-case scenario for
residue depletion.
Calculating a Withdrawal Period for Edible Tissues
The EMEA published a guidance document on the establishment of withdrawal
periods for edible tissues of food-producing animals (EMEA-CVMP, 1997 ). At the
time of publication, three approaches to calculating withdrawal periods were used
in Member States of the EU. The simplest method involved setting the withdrawal
period at the time when residues in all tissues have depleted to below the respective
MRL. An extension of this method involved addressing large variations in the
280 P.T. Reeves