Total Excipient Control: A Pathway to Increased Patient Safety

The author focuses on how industry can build a system for Total Excipient Control.
Apr 01, 2011
Volume 2011 Supplement, Issue 2

Excipients are used in almost all approved drug products in some way and are essential to the performance of the product. Most excipients used in pharmaceutical products are manufactured to comply with pharmacopeial standards and are used in multiple products. Excipients vary from active pharmaceutical ingredients (APIs) because they are used in many drug products and have different functional characteristics depending on the particular formulation.

Current IPEC guidelines and excipient controls

The International Pharmaceutical Excipients Council of the Americas (IPEC-Americas) is an organization representing makers, distributors, and users of pharmaceutical excipients. IPEC–Americas is a member of the recently established IPEC Federation. The federation was formed in 2010 to coordinate IPEC's global activities in the areas of compendial harmonization, excipient guideline/standard development, and coordination of excipient supply-chain security initiatives with regulatory agencies throughout the world. The federation's current membership is made up of IPEC–Americas, IPEC–Europe, IPEC–Japan, and IPEC China.

IPEC–Americas has also formed two partnerships in Latin America to allow that region's growing pharmaceutical and excipient industry to participate in IPEC activities. The partnerships also allow the Latin American pharma and excipient industry to use IPEC guidelines to improve drug quality and protect patients.

Table I: IPEC Excipient guidelines and whitepapers available on
IPEC has developed guidelines, programs, and proposals on various aspects of excipient control during the past 20 years. Each guideline fills a specific need related to an area of excipient control (see Table I). These guidelines and whitepapers have been used by many companies and regulators to establish appropriate standards for excipient control throughout the world.

IPEC's efforts to assist the Pharamcopeial Discussion Group (PDG) with monograph harmonization has also helped to establish scientifically justified test methods and specifications for pharmacopeial excipients that can be used globally. Many IPEC proposals have resulted in providing the key excipient information and expertise needed to modernize and harmonize existing monographs in the United States Pharmacopeia–National Formulary (USP–NF), European Pharmacopeia (PhEur), and the Japanese Pharmacopeia (JP) to meet today's standards of quality.

IPEC developed an Excipient Safety Guideline (FDA participated on the committee as an advisor) that was published in 1996 in Regulatory Toxicology and Pharmacology (1) to provide guidance on how the safety of new excipients should be evaluated. FDA then published its own guidance document in 2005 titled, Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients, which was based on much of the work done to develop the IPEC guideline and is now the standard for how FDA assesses the safety of new excipients when used in a dosage form (2).

IPEC also recently collaborated with FDA to implement a New Excipient Safety Evaluation Procedure. The procedure provides a mechanism for independently assessing a new excipient for safety and to establish an initial precedence of use (3).

IPEA third-party auditing and certification

Recognizing the importance of supplier qualification and auditing to improve supply-chain security, IPEC established the International Pharmaceutical Excipients Auditing (IPEA) in 2001 to perform qualified third-party audits of excipient manufacturers for which the audit reports can be shared with user companies throughout industry. In 2010, IPEA went through an intensive ANSI qualification program that resulted in IPEA becoming the first independent, ANSI-accredited organization that can perform qualified third-party audits and certifications of excipient manufacturers and distributors.

The formation of IPEA and its recent ANSI accreditation represent a major step forward in providing the industry with an alternative for obtaining GMP audit information from suppliers. Some excipient users find that suppliers are not willing to let them perform an audit if they purchase a small amount of the excipient. In other situations, the supplier may not be willing or have the capabilities to host an audit for every customer. That same supplier may, however, be willing to host an IPEA audit or become certified by IPEA as a means of providing qualified GMP audit information to multiple customers at a reduced cost.

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