Annex 4 WHO guidelines for sampling of pharmaceutical ...

1 59 World Health OrganizationWHO Technical Report Series, No. 929, 2005 Annex 4 WHO guidelines for sampling of pharmaceuticalproducts and related of and types of pharmaceutical products and for and for operation and and on receipt (for acceptance) in the manufacturing process and bulkpharmaceutical materials (primary and secondary) plans for starting materials, packaging materials andfinished products78 Bibliography78 Appendix 1 Types of sampling tools80 Appendix 2 Sample collection form85 Appendix 3 Steps to be considered for inclusion in a standard operating procedure8760 Appendix 4 Examples of types of containers used to store samples of startingmaterials and bulk products91 Appendix 5 Examples of use of sampling plans n, p and guidelines are primarily intended for use by governmentalorganizations, such as drug regulatory authorities (includinginspectorates)

2 , quality control laboratories and customs andpolice officials, but some of the general principles may also be appro-priate for application by procurement agencies, manufacturers guidelines should be useful when surveying the national mar-kets for the quality of drug products in accordance with national drugquality surveillance programmes for marketed products, whether reg-istered for sale or compounded in choice of a sampling plan should always take into considerationthe specific objectives of the sampling and the risks and consequencesassociated with inherent decision errors. The bibliography at the endof this Annex should be consulted when justifying a sampling plan fora given considerationsSampling comprises the operations designed to select a portion of apharmaceutical product (for definition, see glossary) for a definedpurpose.

3 The sampling procedure should be appropriate to the pur-pose of sampling , to the type of controls intended to be applied to thesamples and to the material to be sampled. The procedure should bedescribed in operations related to sampling should be performed with care,using proper equipment and tools. Any contamination of the sampleby dust or other foreign material is liable to jeopardize the validity ofthe subsequent definitions given below apply to the terms as used in these guide-lines. They may have different meanings in other sampleWhatever total quantity of sample materials is quantity of any drug produced during a given cycle of the manufacturing process is continuous, the batch originates in adefined period of time during which the manufacturing conditions arestable and have not been sampleSample resulting from combining all or parts of two or more samplesof the quantity of a bulk starting material, or of a drug product, made byone manufacturer or supplied by an agent, and supplied at one time inresponse to a particular request or order.

4 A consignment may com-prise one or more lot-identified packages or containers and mayinclude material belonging to more than one lot-identified sampleSample ready for the application of the test material is regarded as homogeneous when it is all of the sameorigin ( from the same batch) and as non-homogeneous when it isof differing sampleSample collected directly from the productAny material1 or product intended for human or veterinary use pre-sented in its finished dosage form or as a starting material for use insuch a dosage form, that is subject to control by pharmaceuticallegislation in the exporting state and/or the importing activities undertaken in defining a product or service need, seek-ing expressions of interest from enterprises to supply the product orservice, and examining the product or service offered against thespecification, and the facility where the product or service is preparedagainst common standards of good manufacturing practice (GMP).

5 The examination of the product or service and of the facility where itis manufactured is performed by trained and qualified inspectorsagainst common standards. Once the product is approved, and thefacility is approved for the delivery of the specified product or service,other procurement agencies are informed of the approval. Pre-qualification is required for all pharmaceutical products regardless of1 Material is used in the document for pharmaceutical products and related materials .63their composition and place of manufacture or registration, but theamount and type of information requested from the supplier for usein the assessment by the procurement agency may operations involved in the preparation of a pharmaceutical prod-uct, from receipt of materials, through processing, packaging andrepackaging, labelling and relabelling, to completion of the sampleSample in which the different fractions of the material have an equalprobability of being sampleSample obtained according to a sampling procedure designed to en-sure that the different parts of a batch or the different properties of anon-uniform material are proportionately sampleSample collected as part of the original sampling process and reservedfor future testing.

6 The size of a retention sample should be sufficientto allow for at least two confirmatory analyses. In some cases statu-tory regulations may require one or more retention samples, each ofwhich should be separately identified, packaged and portion of a material collected according to a defined samplingprocedure. The size of any sample should be sufficient to allow allanticipated test procedures to be carried out, including all repetitionsand retention samples. If the quantity of material available is notsufficient for the intended analyses and for the retention samples, theinspector should record that the sampled material is the availablesample (see sampling record) and the evaluation of the results shouldtake account of the limitations that arise from the insufficient responsible for performing the sampling methodThat part of the sampling procedure dealing with the method pre-scribed for withdrawing planDescription of the location, number of units and/or quantity of mat-erial that should be collected, and associated acceptance procedureThe complete sampling operations to be performed on a definedmaterial for a specific purpose.

7 A detailed written description of thesampling procedure is provided in the sampling recordWritten record of the sampling operations carried out on a particularmaterial for a defined purpose. The sampling record should containthe batch number, date and place of sampling , reference to the sam-pling protocol used, a description of the containers and of the materi-als sampled, notes on possible abnormalities, together with any otherrelevant observations, and the name and signature of the unitDiscrete part of a consignment such as an individual package, drum sampleSample obtained according to a sampling procedure designed to se-lect a fraction of the material that is likely to have special selected sample that is likely to contain deteriorated, contami-nated, adulterated or otherwise unacceptable material is known as anextreme starting material may be considered uniform when samples drawnfrom different layers do not show significant differences in the qualitycontrol tests which would result in non-conformity with following materials may be considered uniform unless there aresigns to the contrary: organic and inorganic chemicals; purified natu-ral products; various processed natural products such as fatty oils andessential oils; and plant extracts.

8 The assumption of uniformity isstrengthened by homogeneity, when the consignment is derivedfrom a single of samplingSampling may be required for different purposes, such as pre-qualification; acceptance of consignments; batch release testing;65in-process control ; special controls; inspection for customs clearance,deterioration or adulteration; or for obtaining a retention tests to be applied to the sample may include: verifying the identity; performing complete pharmacopoeial or analogous testing; and performing special or specific and types of pharmaceutical products and relatedmaterialsThe materials to be sampled may belong to the following classes: starting materials for use in the manufacture of finished pharma-ceutical products; intermediates in the manufacturing process ( bulk granule); pharmaceutical products (in-process as well as before and afterpackaging); primary and secondary packaging materials; and cleaning and sanitizing agents, compressed gases and other pro-cessing facilitiesSampling facilities should be designed to: prevent contamination of the opened container, the materials andthe operator; prevent cross-contamination by other materials, products and theenvironment; and protect the individual who samples (sampler) during the possible, sampling should be performed in an area or boothdesigned for and dedicated to this purpose, although this will not bepossible where samples are required to be taken from a productionline ( in-process control samples).

9 The area in which the samplewas taken should be recorded in the sampling record and a sequentiallog should be kept of all materials sampled in each from large containers of starting material or bulk productscan present difficulties. Whenever possible, this work should be car-ried out in a separate, closed cubicle within the warehouse, to reducethe risk of contamination ( by dust) of either the sample or thematerials remaining in the container, or of materials should be sampled in special or dedicated environ-ments ( when sampling articles for which contamination with dirt66or particles from the environment should be avoided, such as aerosolvalves, hormones and penicillins).Generally, taking the original sales pack as a sample from outlets suchas pharmacies or hospitals does not present problems.

10 However, theinspector should ensure that the quantity of sample taken is sufficientfor the intended analyses and for the retention samples, and that allunits sampled are derived from the same batch and preferably fromthe same for samplingThose responsible for sampling procedures include: governmental organizations, such as drug control authorities (in-cluding inspectorates); quality control laboratories; customs andpolice authorities responsible for the clearance of drug productsheld in quarantine after manufacture or importation, and for thedetection of pharmaceutical products that have deteriorated orhave been contaminated, adulterated or counterfeited; customers such as governmental or nongovernmental agencies in-volved in the acquisition of drug products; and manufacturers in the context of good manufacturing practices(GMP).