Why IPEC-Americas Is Needed:

Under U.S. law, a new pharmaceutical excipient, unlike an active drug, has no regulatory status unless it can be qualified through one or more of the three approval mechanisms available for components used in finished drug dosage forms, e.g.:

• GRAS determination pursuant to 21 CFR 182, 184, and 186;
• approval of a food additive petition in 21 CFR 171; and
• as contained in an NDA approval for a specific drug product and for a particular function or use in that dosage form.

All three mechanisms are time consuming, inordinately expensive, and have become increasingly complex in recent years. None has a formal safety evaluation process or suitable approval process specifically for excipients.

In addition, varying national drug registration or approval systems and differences in excipient monograph specifications among the three major pharmacopoeias, the PhEur, JP, and USP make it virtually impossible to produce a single finished drug formulation that can be marketed on a global basis.

This situation is unlikely to change until:

• National drug approval systems are expanded to permit reasonable procedures for acceptance of new excipients and new excipient uses;beginning with how they are produced through recognized good manufacturing practices standards; 
• An appropriate system exists for qualifying excipient suppliers and their products;
• Harmonization of compendial standards for more widely used pharmaceutical excipients is achieved among the major pharmacopoeias; and
• There is mutual recognition and mutual acceptance of pharmaceutical safety and effectiveness data from other national systems among the industrialized countries.

These, as noted earlier in the IPEC-Americas Mission Statement, are major Council goals.

Why We're Different:

Unlike PhRMA, GPhA, CHPA, and other U.S. industry associations whose primary focus is on the action of finished drugs and pharmacologically active ingredients and whose principal members are manufacturers and marketers of final pharmaceutical dosage forms, IPEC-Americas members also include firms that make bulk excipients that go into a finished drug product.

This unique partnership of makers, suppliers and users of drug components works well in IPEC-Americas in part because of the relationship which frequently exists between international pharmaceutical marketers and their counterparts among multinational suppliers of excipients for global use. Often, the impetus to qualify an excipient for a new use in pharmaceuticals or in a new or different dosage form can lead to joint ventures between the producers and potential formulators for necessary testing & submission of data to U.S. and other national regulatory authorities. Cooperation, therefore, is based on the shared goal of both users and producers to qualify a single formulation for marketing in many countries.

What IPEC-Americas Is Doing For Its Member Companies:

Excipient GMP Assessment

Background: In 1995, IPEC-Americas, IPEC Europe, and their member companies jointly adopted, published and implemented for the first time, industry developed good manufacturing practice standards for bulk pharmaceutical excipients. These were the result of a three year effort in consultation with US and European regulatory authorities and their counterparts at the World Health Organization (WHO). This later led WHO to adapt the IPEC guidance for use by its national member states and, following release of updated IPEC guidance in 2001, for the United States Pharmacopoeia to include it as a general chapter in USP/NF, e.g., <1078>.

Later, beginning in 2003, IPEC-Americas and IPEC Europe entered into an arrangement with the Pharmaceutical Quality Group, an organizational unit of the Institute of Quality Assurance, an industry association headquartered in the United Kingdom, to produce appropriate new and updated standards for the manufacturing of excipients for pharmaceutical use. This was published jointly by the three participating organizations in January 2006 and already is being widely used on a global basis. World Health Organization authorities are reviewing the guidance to update present WHO guidance and European Union regulators are considering its use as a standard to implement GMP requirements for certain excipients produced or sold in European Community countries. USP also has indicated that it intends to update its general chapter <1078> to include the new information.

Good Distribution Practices: This document, also a joint project of IPEC-Americas and IPEC Europe, was written to provide guidance for companies involved in the pharmaceutical excipient supply chain. It includes examples based on practical experience and reflects the ongoing concern about possible attempts to contaminate the global drug supply for purposes of terrorism. Because of this, the guide provides additional explanatory notes to the World Helath Organiztion technical report entitled "Good Trade and Distribution Practices for Pharmaceutical Starting Materials" (2003). The IPEC Good Distribution Practices Guide for Pharmaceutical Excipients was published in January 2006 and will be updated on an as needed basis to reflect any changes in global distribution practices throughout the pharmaceutical supply chain.

Other Related Guidance: Also available through IPEC-Americas are both a Significant Change Guide and a Certificate of Analysis Guide for Bulk Pharmaceutical Excipients. The first is designed to establish uniform considerations for evaluating the significance of changes involving the manufacture of excipients and to determine the need for informing the excipient customer and regulatory authorities about the nature of the changes. The COA Guide standardizes the content and format of an excipient certificate of analysis. It also defines the roles and responsibilities of those who produce or distribute excipients or distribute excipients for pharmaceutical use, as well as for those who use them in the manufacture of finished drugs. Both guides have been proposed for publication in USP/NF as general chapters and are scheduled for inclusion in USP31/NF26 which will take effect May 1, 2008.

Work on other future IPEC-Americas and possibly IPEC member documents also is underway. One effort concerns specification development and the process by which an excipient producer and his customer can agree on the specifications of a product to be produced and purchased for a particular purpose and/or funcion in a specific finished pharmaceutical dosage form. Representatives of over 15 member companies are engaged in the project, which is expected to continue throughout 2007.

One phase of the project, however, was completed in 2005. This involved publication of a Standardized Excipient Information Protocol User Guide which lays out standards for the exchange of data between an excipient supplier and companies which are considering use of a supplier's excipient in a finished drug product.

The EIP package includes a site quality overview, a product regulatory datasheet and a site and supply chain security overview. Each document is organized much like a material safety data sheet with separate sections that include specified data and which can be adapted to fit specific user needs or product characteristics.

Related complementary regulatory reference information also is available on the Regulatory Reference webpage which lists links to various regional regulatory websites.

3rd Party Auditing: The keystone of the ongoing supplier assessment program involves auditing the manufacturing practices and processes of excipient suppliers and distributors. Auditing began in April 2002 and has grown every year since, along with a new program which involves auditor training. In 2010 IPEA became accredited by ANSI (American National Standards Institute) to offer Excipient Certification. For more information, please visit the IPEA website at www.ipeainc.com.

Excipient Safety Evaluation Guidance:
Safety Evaluation Guidelines developed and originally adopted in 1995 by IPEC-Americas apply to the primary routes of administration. Similar guidelines were published by IPEC Europe in January 1998. Both were reviewed in 2002 and updated.

The guidelines are presented in a tiered approach of recommended data that should be available on an excipient to provide a pharmaceutical formulator with a rational basis for including a new excipient in a drug formulation and have been evaluated by U.S., European, and Japanese regulatory agencies. In fact, much of what is in the IPEC guide is included in current FDA guidance entitled Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients.

Industry Meetings and Conferences
As the need has arisen since its founding, IPEC-Americas has continued to produce workshops and industry-wide conferences that address important regulatory affairs and compendial issues. The most recent conference celebrated the 20th Anniversary of IPEC and took place in early 2011 in Baltimore, Maryland.

Pharmacopoeial Harmonization Projects
IPEC committees and technical working parties from the three principal regions, e.g., the Americas, Europe, & Japan, have developed and submitted proposed monographs for a number of excipients identified by the major compendia as priority candidates for harmonization. Some industry submissions have been recommended for acceptance by one or more committees of revision and others are under review by pharmcopoeial committees.

Currently, IPEC-Americas subcommittees are working to harmonize numerous important excipient materials that include several cellulose derivatives, gelatin, glycerin, magnesium stearate, the parabens, polyethylene glycol, the polyols, starches and titanium dioxide. Special working groups studying heavy metals-related issues and others that involve method validation also are active.