Excipient Quality system

ISO certification for excipient manufacture is increasingly being required by final dosage formulators in the USA, Europe and Japan. Thus, compliance to ISO 9000 can confer greater acceptability of a supplier s excipients in world markets. There is additional value to applying the principles of ISO 9000 to excipient manufacture since excipient quality system measures enhance GMPs. Such ISO considerations as conformance to specific customer requirements, purchase of raw materials and statistical techniques have benefit for both the excipient customer and the excipient manufacturer, and strengthens the relationship between the two. 

Section 4, Excipient Quality Systems, addresses the requirements necessary for compliance with relevant GMP principles and implementation of an excipient quality system. This section also recommends measures to limit excipient contamination. 

Manufacture of excipients in compliance with excipient GMP requirements is based upon an International Organization for Standardization (ISO) 9001 compliant quality system as the foundation to which additional GMP requirements are added. If the manufacturer of the excipient chemical has achieved certification to ISO 9001, then the specific GMP requirements can be added to the quality system already in place. Otherwise, all manufacturing-related ISO 9001 requirements should be implemented in an ISO compliant manner. Therefore such ISO requirements as a sound document... 

This chapter will focus on those additional GMP requirements for the manufacture of excipient ingredients under an ISO 9001 compliant quality system. While certification to ISO 9001 is unnecessary for compliance to excipient GMPs, many of the manufacturing-related requirements as noted above are essential for adequate GMP conformance. With the numerous ISO 9001 compliance resources available, this chapter will assume the reader has the knowledge to implement those relevant general ISO 9001 requirements. 

Excipients can be crucial determinants of product performance and quality. Thus, they should be sourced directly from a reputable vendor who has quality systems in place to ensure consistent manufacture and control. Procurement from brokers is to be discouraged. Auditing such providers for the presence of quality systems and controls should be the norm, particularly if they are new suppliers to the pharmaceutical industry. A validation program should be put in place to establish reliability of the supply source. This program should take the following into account ... 

A formal quality policy should be established and implemented company-wide by excipient manufacturers. Management should be committed to this policy and should appoint appropriate company personnel to be responsible for coordination and implementation of the quality system. Management should participate in the development of the company s quality policy and provide the resources necessary for development, maintenance and periodic review of such a policy and quality system. 

The excipient manufacturer should have a system to control all documents and data that relate to the requirements of the quality system. Documents and subsequent changes to the documents should be reviewed and approved by designated personnel before issuance to the appropriate areas identified in the documents. A record should be kept of where the controlled documents are located. The control should assure the issuance and removal of the appropriate document to the areas previously identified. 

This guide is applicable to the manufacture of all excipients intended for use in human drugs, veterinary drugs and biologies. It covers the quality systems and the extent of GMP necessary throughout the chain of production up to and including delivery to customers. 

The quality system standard chosen as a framework for this guide is ISO 9002, which is appropriate to manufacturing. Requirements specific to excipients have been added. 

The revised ISO 9002 (July 1994) numbering system has been adopted throughout this document because many suppliers already use the standard as a basis for their quality system, including those companies which already have third party certification. Requirements specific to the manufacturing of excipients have been included under each of the ISO headings. 

Section 3, the General Guidance section, provides an overview of the appropriate GMP criteria applicable to excipient manufacture, the relationship of excipients to finished dosage forms, and the point of application of excipient GMPs and quality systems. 

This GMP guide should be the basis for the quality system in the manufacture of excipients. Procedures which are utilized in the manufacture and control of excipients should be written. Conformance to those procedures should be documented. The procedural system should have adequate formal controls related to procedure approval, revision, and distribution. These controls... 

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