This article is part of PharmTech's supplement "Solid Dosage and Excipients 2010."
During a series of discussions with the US Food and Drug Administration in 2008, it was expressed to IPEA representatives that excipient GMP conformance certification could have benefits to the excipient and pharmaceutical industry beyond the existing IPEA audit program. Certification assures excipient manufacturers that they are in substantial conformance with IPEC/Pharmaceutical Quality Group (PQG) excipient GMP guide, a recognized global document for excipient manufacturers. (2). Accreditation of IPEA provides additional assurance to FDA and pharmaceutical customers that conformity assessment of the excipient manufacturer was performed in accordance with Guide 65 requirements and that the excipient supplier meets appropriate GMP requirements. However, it is worth noting that the customer or end user remains obligated to assure excipient quality in terms of meeting compendial and mutually agreed-upon specified requirements.The certification process
Excipient GMP Conformance Certification is open to all excipient manufacturers whether or not the excipient is compendial. The certification process for a typical excipient is based on a comprehensive site audit that ordinarily requires two auditors two days to complete. Off-site operations and other complexities may add to the audit time allocated. A Certification Audit Report is written, reviewed by IPEA Executive Management, and provided to the excipient manufacturer to confirm accuracy of the audit observations. The excipient manufacturer is encouraged to submit a corrective-action plan describing the remediation of adverse findings. The Certification Audit Report, along with the corrective-action plan, is then submitted to the IPEA Certification Board for consideration. Certification decisions are made by consensus of the ad hoc Certification Board, which is comprised of four excipient and pharmaceutical industry experts. Upon certification, a certificate is issued, and the excipient manufacturer, site, and excipient name are posted to the IPEA certification website.
IPEA offers the pharmaceutical customer the opportunity to review the basis upon which certification has been granted. The certification audit report is available for sale at nominal cost with the majority of the proceeds applied to the excipient manufacturer's annual certification fee.
Surveillance and recertification
Guide 65 requires that IPEA conducts surveillance audits of excipient operations to assure customers and regulators that the excipient supplier maintains GMP conformance. Although certification covers a period of two years, IPEA performs annual surveillance audits to follow up on previous audit findings and the implementation of corrective actions and to assess changes to the site quality system. IPEA also audits one-half of the quality system against excipient GMP requirements. Upon completion of the second surveillance audit, IPEA combines the two surveillance audit reports and issues a recertification audit report to the IPEA Certification Board. With Board concurrence, IPEA recertifies the site for another two years.
IPEA may suspend or revoke certification at any time if made aware of deviations to GMP. Such information is obtained from IPEA surveillance audits, regulatory or customer inspections, or complaints.
Critical Guide 65 requirements for accreditation of a certification body such as IPEA include:
Typically, ANSI Product Certification Accreditation uses an auditable standard as the basis for certification. Because there is no excipient GMP standard, IPEA issues certification to the current IPEC–PQG excipient GMPs (2). To compensate for the lack of a standard, IPEA established objective conformance criteria for excipient GMPs against which the excipient site is assessed.
The ANSI-accredited product conformity program must operate under a documented quality system. IPEA developed a quality system for the certification program with a quality manual that describes the principles of compliance to Guide 65 requirements and procedures that detail conformance activities. Records were established to demonstrate compliance with those procedures.
ANSI Conformity Assessment programs are required to operate without discrimination and are accessible to all applicants. IPEA met this requirement with a commitment to administer the program without prejudice. Although undue financial conditions can present an obstacle to accessibility, IPEA mitigated this concern by offering the audit report to the pharmaceutical user at nominal cost and with most of the financial benefit given to the applicant to offset the ongoing cost of certification.
Of particular concern to FDA and ANSI, as well as the pharmaceutical industry, is demonstration of impartiality of certification decisions through prevention of conflict of interest. IPEA stipulates that no individual involved in a specific excipient certification can have any incentive to certify the company (e.g., financial interests or as a consequence of past employment, consulting arrangement, or family employment). The composition of the four-member Certification Board is such that no portion of the industry, excipient maker or user, dominates. Finally, conformance to procedural requirements concerning conflict of interest is stipulated by contract between IPEA and consultants that requires conformance by the auditor, Certification Board members, and IPEA executives.