Quality Assurance of Pharmaceuticals - A Compendium of Guidelines and Related Materials - Volume 1
(1997; 248 pages) [French] View the PDF document
Table of Contents
Open this folder and view contentsIntroduction
Open this folder and view contents1. National drug regulation
Open this folder and view contents2. Product assessment and registration
Open this folder and view contents3. Distribution
Open this folder and view contents4. The international pharmacopoeia and related activities
Open this folder and view contents5. Basic tests
Close this folder6. Laboratory services
Open this folder and view contentsNational laboratories for drug quality surveillance and control1
Open this folder and view contentsGood laboratory practices in governmental drug control laboratories1
Close this folderSampling procedure for industrially manufactured pharmaceuticals1
Open this folder and view contents1. General considerations
Open this folder and view contents2. Use of terms
View the document3. General precautions to be taken during sampling operations
View the document4. Packaging and labelling of samples
View the document5. Sampling during pharmaceutical inspections
View the document6. Sampling of pharmaceutical dosage forms in regular surveillance programmes on drug quality during marketing
View the document7. Sampling of pharmaceutical dosage forms for acceptance of consignments
Close this folder8. Sampling of starting materials
View the document8.1 General considerations
View the document8.2 Sampling plans for consignments of starting materials supplied in several sampling units
Open this folder and view contents7. International trade in pharmaceuticals
Open this folder and view contents8. Counterfeit products
Open this folder and view contents9. Training
View the documentSelected WHO publications of related interest
View the documentBack cover
 
8.2 Sampling plans for consignments of starting materials supplied in several sampling units

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

Value of n, p or r

Values of N

 

n plan

p plan

r plan

2

up to 4

up to 25

up to 2

3

5-9

26-56

3-4

4

10-16

57-100

5-7

5

17-25

101-156

8-11

6

26-36

157-225

12-16

7

37-49

 

17-22

8

50-64

 

23-28

9

65-81

 

29-36

10

82-100

 

37-44

 

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