Utilizing the full excipient control toolkit
In recent years, IPEC worked to pull together its various guidelines to create an Excipient Qualification guideline. The 2008
guideline provides overall guidance on how to use a number of related IPEC guidelines to build a credible excipient qualification
program from both the maker's and the user's perspective.
As IPEC moves into its third decade, the council is taking this concept further to develop a system of Total Excipient Control
(TEC). The system will use all existing IPEC guidelines, programs, and proposals to build an overall control system from the
time an excipient manufacturer thinks of marketing a chemical as an excipient to the pharmaceutical manufacturing industry's
use of that excipient to the time the patient takes the drug product containing the excipient.
The TEC system involves three areas of control: excipient design, excipient safety, and excipient manufacturing process control
and distribution (see Figure 1). Excipient design controls address setting design criteria in a way that meets the perfromance
requirements for the intended use. The controls also take into account quality-by-design (QbD) principles.
Figure 1: Total Excipient Control (TEC) involves control in three main areas to maximize patient safety. QA is quality assurance.
Ensuring excipient safety involves using information that has been developed to support the safe use of the excipient in the
intended application at the levels of use expected to be experienced by the patient. Excipient manufacturing process control
and distribution is the area of control traditionally covered by GMPs, auditing, quality-control testing, information-sharing,
and supply-chain security.
As part of developing the TEC process, IPEC has identified some areas that are not fully covered by current IPEC guidelines
and programs. The following sections of this article provide some details related to IPEC's plans in this regard.
Validation versus process capability. Validation is one of the most commonly misunderstood issues that comes up during pharmaceutical company audits of their supplier's
excipient manufacturing facilities. Pharmaceutical company auditors often ask excipient manufacturers for their validation
data on the manufacturing or cleaning process and do not always get the information they are looking for because excipient
manufacturers do not always have formal validation studies compiled in the manner typical of the pharmaceutical industry.
In many cases, the problem is tied to the terminology rather than an actual issue of control.
Excipient manufacturers typically have a huge amount of process-capability data that is essentially the same type of data
that a pharmaceutical company would call "validation data," but it is often stored in sophisticated large-scale computerized
process-control systems in a different format from that usually used by the pharmaceutical industry. Sometimes, due to terminology
differences during the audit, the excipient company doesn't realize that this information is what the pharmaceutical auditor
needs. Process-capability data can, however, provide appropriate excipient control and, in many cases, can provide information
far beyond what is typically obtained in pharmaceutical validation studies.
To address this common misunderstanding, IPEC is drafting an Excipient Validation Guide which will clarify how validation
studies should be handled for excipients. This guide will help excipient manufacturers convert their process capability data
into useable information that will provide pharmaceutical users with a better understanding of how the excipient processes
are controlled. Ideally, this guideline will lead to fewer unnecessary observations during audits of excipient manufacturing
operations and help excipient manufacturers better understand what type of validation or process-capability information they
should have in place.