Test Requirements - Starting and Packaging Materials:
17.13 Before releasing a starting or packaging material for use, the QC manager should ensure that the materials have been tested for conformity with specifications for identity, strength, purity and other quality parameters.
17.14 An identity test should be conducted on a sample from each container of starting material (see also section 14.14). It is permissible to sample only a proportion of the containers where a validated procedure has been established to ensure that no single container of starting material has been incorrectly labelled. This validation should take account of at least the following aspects:
– The nature and status of the manufacturer and of the supplier and their understanding of the GMP requirements;
– The QA system of the manufacturer of the starting material;
– The manufacturing conditions under which the starting material is produced and controlled;
– The nature of the starting material and the medicinal products in which it will be used. Under such a system it is possible that a validated procedure for exemption from the requirement for identity testing of each incoming container of starting material could be accepted for the following:
– Starting materials coming from a single product manufacturer or plant; or
– Starting materials coming directly from a manufacturer, or in the manufacturer’s sealed container where there is a history of reliability, and regular audits of the manufacturer’s QA system are conducted by the purchaser (the manufacturer of the medicinal product) or by an officially accredited body. It is improbable that such a procedure could be satisfactorily validated for either:
– Starting materials supplied by intermediaries, such as brokers, where the source of manufacture is unknown or not audited; or
– Starting materials for use in parenteral products.
17.15 Each batch (lot) of printed packaging materials must be examined following receipt.
17.16 In lieu of full testing by the manufacturer, a certificate of analysis may be accepted from the supplier, provided that the manufacturer establishes the reliability of the supplier’s analysis through appropriate periodic validation of the supplier’s test results (see sections 8.8 and 8.9) and through on-site audits of the supplier’s capabilities. (This does not affect section 17.15.) Certificates must be originals (not photocopies) or otherwise have their authenticity assured. Certificates must contain at least the following information (7):
(a) Identification (name and address) of the issuing supplier;
(b) Signature of the competent official, and statement of his or her qualifications;
(c) The name of the material tested;
(d) The batch number of the material tested;
(e) The specifications and methods used;
(f) The test results obtained;
(g) The date of testing.
In-Process Control:
17.17 In-process control records should be maintained and form a part of the
batch records (see section 15.25).
Finished Products:
17.18 For each batch of medicines, there should be an appropriate laboratory determination of satisfactory conformity to its finished product specification prior to release.
17.19 Products failing to meet the established specifications or any other relevant quality criteria should be rejected.
Batch Record Review:
17.20 QC records should be reviewed as part of the approval process of batch release before transfer to the authorized person. Any divergence or failure of a batch to meet its specifications should be thoroughly investigated. The investigation should, if necessary, extend to other batches of the same product and other products that may have been associated with the specific failure or discrepancy. A written record of the investigation should be made and should include the conclusion and follow-up action.
17.21 Retention samples from each batch of finished product should be kept for at least one year after the expiry date. Finished products should usually be kept in their final packaging and stored under the recommended conditions. If exceptionally large packages are produced, smaller samples might be stored in appropriate containers. Samples of active starting materials should be retained for at least one year beyond the expiry date of the corresponding finished product. Other starting materials (other than solvents, gases and water) should be retained for a minimum of two years if their stability allows. Retention samples of materials and products should be of a size sufficient to permit at least two full reexaminations.
Stability Studies:
17.22 QC should evaluate the quality and stability of finished pharmaceutical products and, when necessary, of starting materials and intermediate products.
17.23 QC should establish expiry dates and shelf-life specifications on the basis of stability tests related to storage conditions.
17.24 A written programme for ongoing stability determination should be developed and implemented to include elements such as:
(a) A complete description of the medicine involved in the study;
(b) The complete set of testing parameters and methods, describing all tests for potency, purity, and physical characteristics and documented evidence that these tests indicate stability;
(c) Provision for the inclusion of a sufficient number of batches;
(d) The testing schedule for each medicine;
(e) Provision for special storage conditions;
(f) Provision for adequate sample retention;
(g) A summary of all the data generated, including the evaluation and the conclusions of the study.
17.25 Stability should be determined prior to marketing and following any significant changes, for example, in processes, equipment or packaging materials.
References:
1. Good manufacturing practices for pharmaceutical products. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-seventh report. Geneva, World Health Organization, 2003 (WHO Technical Report Series, No. 908), Annex 4.
2. Validation of analytical procedures used in the examination of pharmaceutical materials. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second report. Geneva, World Health Organization, 1992 (WHO Technical Report Series, No. 823), Annex 5.
3. EudraLex – Volume 4. Good manufacturing practice (GMP) Guidelines. European Commission.(http://ec.europa.eu/health/documents/eudralex/vol-4/ index_en.htm).
4. Pharmaceutical Inspection Convention, Pharmaceutical Inspection Co-operation Scheme (PIC/S). In: Guide to good manufacturing practice for medicinal plants. Geneva, PIC/S Secretariat, 2000.
5. Quality assurance of pharmaceuticals. WHO guidelines, related guidance and GXP training modules. Geneva, World Health Organization, 2013 (CD-ROM).
6. Good manufacturing practices for pharmaceutical products, Part one. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-second report. Geneva, World Health Organization, 1992 (WHO Technical Report Series, No. 823), Annex 1; and in: Quality assurance of pharmaceuticals. A compendium of guidelines and related materials. Vol. 2, 2nd updated edition. Good manufacturing practices and Inspection. Geneva, World Health Organization, 2007; and in: Quality assurance of pharmaceuticals. WHO guidelines, related guidance and GXP training modules. Geneva, World Health Organization, 2013 (CD-ROM).
7. Model certificate of analysis. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-sixth report. Geneva, World Health Organization, 2002 (WHO Technical Report Series, No. 902), Annex 10.
WHO Good Manufacturing Practices For Pharmaceutical Products: Main Principles
(Annex 2, WHO Technical Report Series 986, 2014)
