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 took effect May 1, 2008.
Work on other future IPEC member documents 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.
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.
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. IPEC-Americas provides educational programming for ExcipientFest Americas and offers educational webinars and excipient GMP auditor training.
Pharmacopoeial Harmonization Projects
IPEC committees and technical working parties from the global regions 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.