For the excipient survey question, approximately 74% of drug-product manufacturers answered few or none for testing excipient
suitability using experimental-scale (laboratory scale) drug-product batches or pilot-scale manufacturing batches. This result
is not encouraging. Even though the excipient is of compendial quality, not testing the suitability of an excipient(s) procured
from new vendors through laboratory- or pilot-scale experiments may be contributing to difficulties currently encountered
by drug-product manufacturers during production-batch scale-up operations or when an excipient is procured from different
Survey responses showed that, for USP–NF excipients, 88% of excipient manufacturers, 75% of distributors, and 68% of drug-product manufacturers perform additional
functionality or processability testing that is not part of any compendial monograph (e.g., USP–NF, PhEur, JP). About three-fourths (76%) of drug-product manufacturer respondents perform such tests to determine excipient suitability
for their intended use.
FDA's QbD and CGMPs for the 21st Century initiatives and their anticipated impact on improving pharmaceutical product quality
were discussed at the workshop. Workshop participants recognized the value in understanding the physicochemical properties
of excipients that impart their functionality in the drug product, as well as their contribution to the successful manufacturing
of the product. It was noted that there must be early interaction between the drug-product manufacturer and FDA for QbD-based
applications to be successful.
Workshop participants noted that IPEC and USP plan to question the need for PhEur to include the tests for functionality-related characteristics (FRCs) in monographs whether nonmandatory or not. Listing
nonmandatory FRCs in the monograph may provide misleading guidance and could result in drug-product manufacturers not performing
the studies they should to identify the FRCs that matter most in connection with their use of an excipient. It also may increase
the possibility of non–value added testing in the supply chain. Recently Pharmeuropa published a proposed General Chapter 5.15, "Functionality-Related Characteristics of Excipients," which explains the use
of FRCs in PhEur and how tests may be included in monographs (11). Workshop participants agreed that a general information chapter approach
is preferred that does not include the listing of FRCs in monographs.
USP–NF informational chapter ‹1059› "Excipient Performance" provides an overview of the key functional categories of excipients
identified in USP–NF along with tests that relate to excipient performance. Careful consideration of the function of the excipient in the dosage
form and the critical attributes that relate to excipient performance will determine the need for additional tests on the
excipient. The draft of ‹1059› "Excipient Performance" is projected for publication as a Stimuli Article in Pharmacopeial Forum Sept.–Oct. 2007 (PF 33.5). USP's goal is to have the draft available for discussion and feedback. USP emphasizes a distinction in the ‹1059›
information chapter tests (focus on performance testing) and those in a monograph (focus on identity, strength, purity, quality).
The following text from the most current draft of ‹1059› includes such a statement:
This Informational Chapter provides an overview of the key functional categories of excipients identified in USP–NF along
with tests that may relate to excipient performance. This chapter focuses primarily on those tests that are not included as
required tests in compendial monographs (e.g., strength, purity, identity). Careful consideration of excipient function, manufacturing
process, and dosage form performance will allow for the selection of appropriate tests to assure that critical excipient attributes
relating to performance are adequately monitored and controlled.
IPEC foresees a need to continue developing our knowledge and understanding of materials and processes and how they interact
to produce medicines that consistently meet the public's expectations (12). The industry should continue to work with compendia
to establish a harmonized approach for incorporating physical and chemical tests and analytical procedures in the General
Chapters of the pharmacopeias. IPEC does not support the inclusion of these tests into monographs unless they may be needed
to fulfill an identification requirement, (e.g., test for viscosity of a polymer). IPEC believes that the selection of appropriate
performance-related tests be done by appropriate scientific investigation of the excipients used in a specific formulation
in a specific process using specific equipment.