Excipients are an important part of drug products. Unlike APIs, excipients can be single entity substances or multicomponent substances. Additionally, excipients can be plant based or mineral based or synthetic or a combination. Excipients, while potentially complex, are generally considered as safe as many have been in use for decades. In the late 2000's, the FDA requested that the USP embark upon a program to modernize the compendial testing for excipients in the USP/NF. This was based on increase in the number cases of adulteration of actives and excipients. Previous to that, many compendial tests for excipients were wet chemistry or non-specific or visual or lacked good quantitation. Finding new methods that were usable like chromatography was one challenge, but other challenges were encountered related to the new methodologies that could give new insight as to the actual composition of excipients. While a few excipients consist of a single entity, most excipients consist of more than one component. Like APIs, excipients do have impurities that affect the quality of the excipient ("excipient impurities"). However, unlike APIs, excipients typically have other compounds that are a part of the excipient. These are minor components which are part of the excipient but not listed in the name. Added substances that are added to improve the handling processing, performance, or stability of the excipient. A third is concomitant components which are compounds that are in the excipient that may or may not be identified in the definition. It is important to understand the information obtained about an excipient from the new methodology to yield an acceptable monograph. In the case of chromatography, new compounds related to the excipient are usually found. It is likely that the newly discovered compounds have been a part of the excipient all along especially in the case of excipients derived from botanical or mineral sources. Furthermore, some of the compounds that are associated with the nominal component (component named in the title) are important for its functionality in drug product formulations. In many cases, the mechanism by which the concomitant component aids the excipient in its functionality is not known. This effect is different for different formulations as to which combination is responsible for the particular functionality is not usually fully understood either. Therefore, during the development of a new monograph, the effect of the concomitant and minor components for users who have been the excipient previously must be considered. Changes in the functionality of the excipient as a result of a new set of compendial specifications may cause the drug products that use the excipient to no longer be manufactured resulting in patients not being able to get drug products they depend on. Another factor that must be considered is that the excipient may not be available in a different form than what is currently available. Also, the new testing methods may change the quantitation of each component from what was obtained from the old method which requires restating the quantitative specification for the excipient.
Explain the need for use of modern analytical techniques for setting of compendial standards for excipients ahd their release testing.
Explain how APIs and excipients differ with respect to general composition and how the differences affect the compendial specifications for excipients.
Categorize excipients based on the simplified model proposed.
Explain why the compendial tests represent the minimum standard of compliance for an excipient and why further understanding of the excipient in relation to its particular use in a formulation is a requirement for Quality by Design.
Explain why the use of modern analytical techniques increase the knowledge related to the complexity of each excipient and how setting compendial standards based on this knowledge is difficult so as to not disrupt the drug product supply to patients without compromising the safety of the excipients