This article is part of PharmTech's supplement "Solid Dosage and Excipients 2010."
International Pharmaceutical Excipient Auditing (IPEA), a subsidiary of the International Pharmaceutical Excipients Council
(IPEC), recently completed the first-ever excipient good manufacturing practice (GMP) certification. At press time, IPEA had
just received a positive decision from the American National Standards Institute (ANSI) to accredit the program. Accreditation
of the program, officially called the IPEA Excipient GMP Conformance Certification Program, by ANSI signifies conformance
to the International Organization for Standardization (ISO)/International Electrotechnical Commission (IEC) Guide 65 on general
requirements for companies and organizations operating product-certification systems (1). Certification to excipient GMP is
a logical extension of the IPEA Excipient Auditing Program, which launched in 2001.
LOGO COURTESY OF IPEA
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:
Certification against an auditable standard
Documented program administration
Nondiscriminatory program management
- Publically accessible program documentation.
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
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.