SAMPLES OF STARTING RAW MATERIALS AND PACKING MATERIALS

I. PRINCIPLE

1. Sampling is an important operation when only a small part of a batch is taken as a sample. Accurate conclusions with regard to the whole batch shall not be based on tests conducted on samples that are not representative. Correct sampling is an integral part of the pharmaceutical quality system. The sampling rules are specified in Items 214 – 217 of these Rules. This Attachment contains additional requirements to samples of starting raw materials and packing materials.

II. STAFF

2. (1) The staff taking samples shall undergo basic training and then shall be periodically trained in disciplines related to correct sampling. This training shall include the following subjects:

the sampling procedure;

sampling instructions approved by the manufacturer;

methods and equipment used for sampling;

the risk of cross contamination;

precautionary measures to be taken for unstable and (or) sterile substances;

the importance of taking into account the results of a visual inspection of the appearance of materials, packages and labels;

the importance of documenting any unexpected or unusual circumstances.

III. STARTING RAW MATERIALS

3. (2) The authenticity of the entire batch of raw materials is generally guaranteed only if individual samples have been taken from all containers and each sample has been tested for identity. It is allowed to take samples only from a number of containers, if there is a validated procedure that guarantees that all containers with starting raw materials have been marked correctly.

4. (3) In case of such validation it is necessary to take into account at least the following aspects:

the data on the manufacturer and supplier (their type and current condition), as well as their understanding of the requirements of these Rules;

the use of a quality management system by the manufacturer of starting raw materials;

the manufacturing environment where starting raw materials are produced and checked;

the nature and properties of starting raw materials and medicines manufactured from them.

5. If there is such a system, a procedure that has been validated and excludes the necessity to conduct authenticity tests of starting raw materials from each received container may be acceptable for:

starting raw materials received from one manufacturer or from one production site;

starting raw materials received directly from the manufacturer or in containers sealed by the manufacturer, and this supplier has a spotless reputation, and if the buyer (the manufacturer of the medicine) or an officially accredited authority conducts regular audits of the manufacturer’s quality management system.

6. This procedure cannot be satisfactorily validated and used for:

starting raw materials supplied by intermediaries, when the manufacturer is unknown or has not been audited;

starting raw materials used for manufacturing parenteral medicines.

7. (4) The quality of the batch of staring raw materials may be assessed by taking and testing a representative sample. Samples taken for authenticity tests may be used for this purpose. The number of samples taken to obtain a representative sample shall be determined statistically and indicated in the sampling plan. The number of individual samples that may be mixed to make an average sample shall also be determined subject to the type of raw materials, the information on the supplier and the homogeneity of the average sample.

IV. PACKING MATERIALS

8. (5) The sampling plan for packing materials shall be drawn up subject to at least the following aspects: the received amount, the required quality, the nature of the material (e.g. primary packing materials and (or) printed packing materials), production methods, as well as the data on the manufacturer’s quality management system for packing materials that are based on the results of conducted audits. The number of taken samples shall be determined statistically and indicated in the sampling plan.