Verification of an excipient's pedigree and comprehensive incoming inspection data are important elements of supply-chain security. Without adequate implementation of both components, a pharmaceutical company can be exposed to nefarious activities comparable to a computer user whose Internet activities are unprotected by a firewall and antivirus software. As demonstrated by recent global supply-chain breaches, excipients are vulnerable to contamination, counterfeiting, and adulteration.
Authenticity and quality
The second step in implementing the checklist involves performing an assessment of the manufacturer to confirm that the excipient was produced using an excipient GMP compliant quality system (2). In addition, each stop in the distribution supply chain must be assessed to confirm that the excipient was handled in compliance with applicable GMP and GDP requirements (3).
Industry best practice is to visit and audit the original excipient manufacturing site. Relying solely on responses from questionnaires no longer meets regulatory expectations under current GMP for supplier qualification. In a recent conference presentation, FDA announced that pharmaceutical users may soon be expected to audit their excipient suppliers themselves or to use a qualified third-party auditor (4). The pharmaceutical user should assess the third-party provider and confirm that it is qualified. At the conference, FDA said pharmaceutical manufacturers would be expected to audit their suppliers or use an accredited third party or qualified third party to do so. The American National Standards Institute (ANSI) has accredited an organization to provide certification to excipient GMPs that is accepted by FDA.
Before any on-site audit, it is advisable to send the supplier a pre-audit questionnaire that includes a request for the manufacturer to list the applicable quality system under which the excipient was manufactured. The pre-audit questionnaire can also facilitate the site audit by providing applicable background information. The questionnaire should identify the scope of operations conducted at the site. For the manufacturer, the response should identify contract operations, which also require auditing.
For the distributor, the response to the pre-audit questionnaire must identify the scope of its operation and whether other on-site operations might affect excipient quality. For example, the distributor may package bulk excipient or repackage excipient into smaller packages. The pharmaceutical manufacturer also must confirm that the distributor samples and tests the excipient to confirm there has been no contamination or degradation of the material. Once the pre-audit questionnaire is completed, the pharmaceutical user can finalize an audit plan and schedule the on-site audit.