The Excipient Information Package, A Win-Win Solution

Excipient questionnaires have long been a thorn in the side of quality groups. Covering everything from feedstock used in the manufacturing process to distribution channels, questionnaires are meant to help an excipient user qualify a vendor or an excipient based on potential risk. Although a necessary and worthwhile endeavor, questionnaires present their own set of challenges.

Excipient questionnaires

The challenge in completing excipient questionnaires is that every excipient user has a unique survey format. Vendors are not only overwhelmed by the number of questionnaires to which they must respond, but the varied survey formats further compound the challenge. The end results are slow response times and a loss of data integrity.

The Standardized Excipient Information Package (EIP) Protocol and EIP.

Quality groups cite other challenges in using surveys for information gathering. Questionnaire items are often focused on active pharmaceutical ingredients instead of excipients. The Standardized Excipient Information Package (EIP) Protocol clearly defines the level of information required at the excipient level.

Change control is another concern. The manufacture of excipients is an evolving industry. The absence of a standardized format impedes the excipient makers' ability to update excipient users of changes that may affect a previously completed questionnaire. This situation affects the integrity of the information transferred.

A solution for information gathering

In early 2006, the International Pharmaceutical Excipients Council (IPEC) addressed the industry-wide dilemma of data integrity by issuing its EIP Protocol. The development of the EIP Protocol was a joint effort of excipient users and makers. The EIP Protocol is now being used by individual excipient makers to create their own EIPs.

Some benefits that may be derived from an industry-wide standardized excipient information process include:

• Excipient users have the ability to receive complete data in a standardized format

• Change control is facilitated through periodic reviews

• The opportunity for electronic-data interchange makes information gathering more pliable and efficient.

Applying technology to what has historically been a labor-intensive process allows excipient makers an opportunity to provide important information to excipient users in real time. Distributors are better able to ensure the integrity of the excipients they supply and the manufacturers they represent.

The value of an EIP

The EIP concept was developed with the primary objective of providing industry standards for the transfer of information from excipient maker to user to simplify and improve the process. It was developed using the collective wisdom of the maker, user, and regulatory communities. Numerous global pharmaceutical company questionnaires were reviewed as part of the development process. Information was included based on the pharmaceutical industry's need for the information.

Regulatory reference page. An accurately prepared EIP is dependent on a correct interpretation of the EIP Protocol. A regulatory reference page is provided on the IPEC–Americas website (ipecamericas.

org) to assist maker companies in preparing the EIP. The regulatory reference page is periodically reviewed and updated as necessary.

Information transfer. The EIP is a very efficient process for the transfer of information as compared with completing a questionnaire. Some companies have elected to maintain the EIP on a website, making the process even more efficient in terms of human resources. Increased efficiency of the process offers an opportunity to potentially reduce the cost of pharmaceuticals for the patient.

The EIP process streamlines the supplier information process for the user by eliminating the work process of developing supplier questionnaires, sending a copy to suppliers at defined frequencies, and tracking the return of completed questionnaires from the suppliers. Turnaround time for EIP requests is remarkably improved vis-à-vis questionnaires. The EIP is often furnished on the same day as the request. Questionnaires, on the other hand, often take many months to receive and may not be fully completed. Missing or improperly completed questionnaires delay the approval process for materials and suppliers.

It is important that information transferred from excipient maker to user is and remains current. The EIP offers an important advantage over completing a questionnaire in this regard. Because the EIP is integrated into the excipient maker's management of change process, maintaining the accuracy of the EIP relies upon a properly functioning quality system. Although sometimes requested by excipient users, questionnaires provide no mechanism for update in the event of changes. The EIP Protocol and the EIP are version controlled, with an established revision process for the EIP Protocol to ensure that information provided in the EIP remains current.

EIP format. The EIP is provided in a standardized format similar to a material safety data sheet, which facilitates preparation, maintenance, and use of the information. The EIP documents are meant to be used by individuals experienced and competent in evaluating excipient suppliers and are not intended as a replacement for audits. The EIP Site Quality Overview, however, may be used as an adjunct to audits for vendor qualification and ongoing assessment. Additionally, the Site Quality Overview could minimize the time needed for an onsite audit. By serving as a conduit to notify excipient user companies of changes, maintenance of an EIP may reduce the frequency of on-site audits under appropriate conditions.

Excipient manufacturers

From the excipient manufacturer's perspective, the challenge of receiving, completing, and returning numerous customer questionnaires is daunting. Each questionnaire is formatted differently. Questions are sometimes difficult to understand and therefore, difficult to answer properly. Most importantly, because of the manual nature of the process, the hand-completed documents are typically not incorporated into the excipient manufacturers' quality management system.

The EIP concept was developed as a way to elevate the transfer of information from supplier to customer (maker to user) from an inadequate process to a system of reliable, peer-reviewed documents that are managed with the quality system.

The EIP is an integral part of the excipient maker's quality management system. As such, users can be assured that EIPs are prepared by qualified professionals and are internally reviewed for accuracy. EIPs are document-controlled with periodic review, and any changes or updates are managed through revision history and version control. The integration into the quality management system and the management of change process ensures that the EIP is always current and meets the needs of the intended target marketplace.

There are other benefits of the EIP process. These include:

• Users can easily compare suppliers on an equal basis because suppliers provide information in a common format

• Users may request EIP updates on an ongoing basis

• Users can quickly identify changes by reviewing the EIP's revision history

• New industry-wide information needs can be incorporated into the EIP Protocol.

Distributors

Although supplier-information requirements are the same for both large and small pharmaceutical customers, it can be difficult to obtain the completed questionnaires necessary to qualify an excipient if volume history or potential is minimal. Distributors routinely facilitate the delivery and follow-up of their customers' questionnaires. The volume of work associated with this customer-service function requires significant resources. The EIP permits the resources that handle this critical customer-service function to provide meaningful information instead of spending hours tracing the whereabouts of a single questionnaire. Increasingly, upon receipt of a questionnaire from a distributor, the targeted manufacturer is able to respond in a timely manner with a product-specific EIP.

Future vision

The future vision of the EIP process is that, as new requirements come along, the EIP Protocol will be updated accordingly. Although IPEC–Americas has led the development of the EIP process, the goal is to harmonize globally, which will further enhance the benefits of the process. The International Pharmaceutical Excipients Council Europe will publish the harmonized version of the EIP Protocol in early 2008. The EIP Protocol for use in Japan will be published by the Japan Pharmaceutical Excipients Council in the fourth quarter of 2007.

David Klug is senior manager of GMP at sanofi-aventis US LLC, david.klug@sanofi-aventis.com and member of the executive committee of the International Pharmaceutical Council of the Americas (IPEC–Americas). Ann Van Meter is a senior quality system specialist with Dow Chemical Company, and Laura Horne is the US account executive (Southeast) for Mutchler Ingredients. All three authors are members of the excipient qualification and GMP committees for IPEC–Americas.