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APPENDIX A A1. Introduction


Many excipients are used in food, cosmetic or industrial products as well as in pharmaceuticals. Thus environmental conditions, equipment and operational techniques employed in excipient manufacture are often those of the chemical industry as opposed to the pharmaceutical industry. Chemical processes can produce impurities from side reactions. Careful process control is therefore essential to minimise levels of impurities and contamination.

Excipients are often manufactured on a large scale utilising continuous processing and automated process controls. Production equipment and processes vary depending on the type of excipient being produced, the scale of production and the type of operation (for example batch versus continuous process).

This appendix is intended to aid in the preparation by an excipient manufacturer for an audit. Both external and internal auditors (see also 8.2.2) will find this appendix useful in identifying the significant issues with respect to GMP and quality that require examination. This section will assist excipient manufacturers in identifying the key deliverables when adopting the GMP standards listed in the other sections of this Guide and help in planning an audit to verify the quality of the excipient manufacturing process and the manufacturer’s quality management system.

For additional information on auditing refer to the IPEC-Americas Good Manufacturing Practices Audit Guideline for Bulk Pharmaceutical Excipients. Also for guidance on the auditing process refer to the IQA PQG Monograph No 5 Pharmaceutical Auditing.

A2. GMP Principles


Control of impurities and contamination In general, the pharmaceutical customer does not perform further chemistry or purification steps on the excipient and it is used as purchased. Consequently, impurities present in the excipient are likely to be present in the drug product. Although dosage form manufacturers have some control over excipient quality through specifications, the excipient manufacturer has greater control over the physical characteristics, quality and the presence of impurities in the excipient they produce.

External contamination of the excipient can arise from the manufacturing environment. However, chemical processes used to manufacture excipients are often performed in closed systems that afford protection against such contamination, even when the reaction vessels are not located in buildings. The external environment may require suitable controls to avoid potential contamination wherever the excipient or in-process material is exposed.


Excipient properties and functionality Excipients are frequently used in different types of drug products where physical characteristics, such as particle size, may be important. While the finished dosage form manufacturer is primarily responsible for identifying the particular physical characteristics needed, it is also the responsibility of the excipient manufacturer to control excipient manufacturing processes adequately to ensure consistent conformance to excipient specifications. Wherever possible, consideration should be given to the end use of the excipient. This is particularly important if the excipient is a direct component of a sterile drug product or one that is claimed to be pyrogen-free.

Copyright © 2006 The International Pharmaceutical Excipients Council and Copyright © 2006 Pharmaceutical Quality Group

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