As already stated, these guidelines are intended primarily for drug control authorities and governmental agencies and are not necessarily appropriate for other parties such as experienced manufacturers with established and time-tested sampling procedures. Manufacturers with limited experience may wish to follow some of these recommendations.

Ideally, each sampling unit should be examined in order to check for intactness or possible damage of the container, and the content should be inspected for uniformity and chemically tested for identity. Uniformity should be tested on selected layer samples at different points of the material without previous intermixing. However, this ideal procedure is not always possible or justified by the purpose of sampling; a number of sampling units should then be randomly selected for sampling. Also it is not prudent to open all containers of products liable to deteriorate under the influence of moisture or oxygen when these are held in a transit warehouse. However, materials in damaged containers or found to be nonuniform must either be rejected or individually sampled for a complete quality control. Unlabelled sampling units must be rejected.

For random sampling, whenever possible each sampling unit is consecutively numbered and the required number of sampling units is then selected at random using tables of random numbers. The number of units depends on different assumptions and three plans in this regard are given below.

Control laboratories of manufacturers are required to analyse and release or reject each received consignment of the starting materials used to produce a drug product. For this purpose they need samples of each sampling unit of a drug substance or a pharmaceutical aid in order to be able to check the identity of the material. These samples subsequently may be pooled in one way or another to perform a full analysis. While for drug substances such a procedure should always be followed, it may be considered not practical or unnecessary for selected pharmaceutical aids.

8.2.1 The “n plan”

The “n plan” should be used with great caution and then only when the material is considered uniform and is supplied from a well-known source. The samples can be withdrawn from any part of the container (usually from the top layer). The “n plan” is based on the formula , where N is the number of sampling units in the consignment. The value of n is rounded up to the next higher integer. According to this plan, original samples are taken from n sampling units selected at random and these are subsequently placed in separate sample containers. The control laboratory inspects the appearance of the material and tests the identity of each original sample according to the relevant specification; if the results are concordant, the original samples are pooled into a final sample from which an analytical sample is prepared, the remaining part being kept as a retention sample. The “n plan” is not recommended for use by control laboratories of manufacturers who are required to analyse and release or reject each received consignment of the starting materials used to produce a drug product.

8.2.2 The “p plan”

The “p plan” may be used when the material is uniform and is received from a source that is well known and when the main purpose is to check the identity. The “p plan” is based on the formula , where N is the number of sampling units. According to this plan, samples are taken from each of the N sampling units of the consignment and placed in separate sample containers. These original samples are transferred to the control laboratory, visually inspected and tested for identity (simplified methods may be used), and, if the results are concordant, p final samples are formed by appropriate pooling of the original samples.

8.2.3 The “r plan”

The “r plan” may be used when the material is suspected to be nonuniform and/or is received from a source that is not well known. The “r plan” may also be used for vegetable drugs as starting materials. This plan is based on the formula, where N is the number of sampling units. Samples are taken from each of the N sampling units of the consignment and placed in separate sample containers. These original samples are transferred to the control laboratory and tested for identity. If the results are concordant, r samples are randomly selected and individually subjected to testing. If the results are concordant, the r samples are pooled for the retention sample.

The accompanying table gives the values of n, p and r according to the different plans.

Values of n, p or r for N sampling units