It is apparent that many generic manufacturers and smaller pharmaceutical companies use means other than physical audit to
qualify their suppliers. An ANSI accredited certification program, therefore, is particularly useful because the program has
been qualified by ANSI and can be so recognized by government agencies. An ANSI accredited certification program, furthermore,
allows pharmaceutical companies to use certification in lieu of site audit for supplier qualification.
Assuring the safety of the drug supply has modified the development of each of these programs. FDA has explicitly stated at
meetings and presentations that shared-audit and third-party audit programs are acceptable as part of a supplier qualification
program (5). Continuing reports of economically motivated adulteration reminds the industry that each site supplying excipients
must be physically audited to ensure conformance to GMP requirements. Supply chain security must begin with a site audit.
Participation by an excipient supplier in any one program can provide adequate assurance of the conformance of the excipient
to GMP because the basis of the audit is the well accepted IPEC-PQG GMP Guide for Pharmaceutical Excipients. As described herein, the Rx–360, EXCiPACT, and IPEA programs each exercise great care in the selection, training, and qualification
of their auditors. FDA has informally stated that these schemes meet regulatory expectations because they have addressed the
issue of auditor competency as a core part of the audit process. Thus the schemes can provide the excipient user with a high
degree of assurance that excipient from suppliers that have participated in a program meet cGMP expectations and will continue
to do so. The cost barrier for this assurance can be greatly reduced by these programs.
These schemes, therefore, can help to ensure patient safety when the drugs that patients consume have been formulated with
excipient components supplied by manufacturers whose facilities have been audited.
Darcy Ewalt is director of divisional GMP auditing at Merck Sharp & Dohme, Corp. (Merck is a member of Rx–360). Tracy L. Cooper, Johnson & Johnson, AD, Consumer Regulatory Compliance (J&J is a member of Rx–360). Frithjof Holtz is quality and regulatory management head of MM-QS Advocacy (EXCiPACT) at Merck Millipore. Irwin Silverstein is vice-president and chief operating officer of International Pharmaceutical Excipients Auditing, Inc.
1. I. Silverstein, Pharm. Technol. 33 (10), 84–88 (2009).
2. FDA, Advisory to Drug and Dietary Supplement Manufacturers, Compounding Pharmacies and Distributors of Excipients and
Dietary Ingredients-FDA Detects High Levels of Peroxide in Crospovidone (Oct. 21, 2010),
3. B. Hasselbalch, "Public Health Challenges for the Quality of Human Drugs," presented at FDA-Xavier University Global
Outsourcing Conference (Cincinnati, June 2010).
4. The Falsified Medicines Directive (FMD) 201⅙2/EU, http://ec.europa.eu/health/files/eudralex/...2011_62/dir_2011_62_en.pdf.
5. See FDA and MHRA presentations at the EXCiPACT launch event in 2012 which are hosted on the EXCiPACT website at