Workshop participants described the expectations of a third-party audit program as including standard operating procedures
that describe program operation, a preaudit questionnaire for the excipient manufacturer, an established audit standard, clearly
identified report content, and a policy for confidentiality of audits. The audit standard must be based on applicable GMPs.
Nicholas Buhay, deputy director, Division of Manufacturing and Product Quality Office of Compliance, Center for Drug Evaluation
and Research, FDA, noted that "FDA is supportive of the Joint IPEC–PQG GMP Guide for Bulk Pharmaceutical Excipients." It should
be noted that USP General Information Chapter ‹1078› "Good Manufacturing Practices for Bulk Pharmaceutical Excipients" is
based on the IPEC–PQG GMP Guide for pharmaceutical excipients.
The third party should be an independent and unbiased organization of auditors, with strong qualifications and a good reputation.
Auditors must be trained in excipient audits and should not audit the site as if it were a facility for the manufacture of
active pharmaceutical ingredients (APIs) or drug products. The third-party audit firm should provide a mock or sample audit
report. Users can qualify a third-party audit program by comparing audit reports for the same excipient with internal audits.
The firm conducting the third-party audit should not consult on the correction of identified issues. There must be a mechanism
to confirm the veracity of the findings, including a review of the excipient manufacturer audit report by the drug-product
During the meeting, excipient manufacturers expressed that widespread use of third-party audit reports may reduce the number
of site audits by customers. Third-party audits would reduce the number of questionnaires from their customers. The pharmaceutical
manufacturers expressed that third-party audits would result in more excipient manufacturers audited thoroughly and completely
because of the additional time that the third party would spend on each audit. This can augment a drug-product manufacturer's
risk management strategy for deciding on which excipient manufacturer to audit, when needed.
The qualifications of the third-party auditor should include training and a general audit background. Qualifications should
include formal recognition such as ASQ certified quality auditor, ISO 9001 certified lead auditor, or other recognized auditor
training course certification. Familiarity with IPEC excipient GMPs is essential along with appropriate audit experience and
background. The qualifications may include experience in API audits and an understanding of the regulatory environment. The
auditor should be knowledgeable about differences between 21 CFR Part 211 and USP General Information Chapter ‹1078›. The auditor should set priorities or categorize audit observations,
know what is important to audit, and know what findings are important. In summary, the auditor must demonstrate audit competency.
The benefits of third-party audits to small drug-product manufacturers include that the audit has more credibility than a
questionnaire alone. Many small drug manufacturers do not have the resources to audit many of their excipient manufacturers
other than the ones they may consider absolutely critical. Because these companies are not able to routinely audit their excipient
manufacturers, they currently only use questionnaires. A concern with solely relying on a questionnaire is not knowing for
certain whether the answers are truthful. Third-party audits may offer a good alternative. With third-party audits, a small
drug-product manufacturer can avoid a staff of auditors, reduce the number of audits (especially outside the United States),
and at the same time have more confidence in their excipient manufacturer. This strategy allows small drug-product manufacturers
to assess more excipient producers more reliably. A small drug-product manufacturer would use the audit to help ensure that
their supplier qualification program is adequate.
Workshop attendees identified International Pharmaceutical Excipients Auditing, Inc. (IPEA) and the USP Pharmaceutical Ingredient
Verification Program as examples of organizations and programs that perform qualified third-party audits.
Strategies to increase the number of excipients labeled USP–NF
This topic was described to the participants as the following:
There is an increasing danger of excipient manufacturers not producing pharmaceutical-grade excipients that meet USP–NF criteria,
which creates an enormous problem for the drug manufacturing industry. This concern is exacerbated by the fact that, USP–NF
is missing monographs for some commonly used excipients. The workshop will assess these issues, and propose solutions to preempt
the issue of reduced numbers of excipients labeled USP–NF.