(344a) Assessing the Adequacy of a Sampling Frequency in the Application of PAT to a Continuous Manufacturing Process for Drug Product

Authors: 
Barnes, L., Eli Lilly & Co.
Hetrick, E., Eli Lilly and Company
Leavesley, I., Eli Lilly & Co.
Shi, Z., Eli Lilly & Co.
The implementation of spectroscopic instruments to determine the concentration of active pharmaceutical ingredient (API) in powder samples is vast and well documented in the scientific literature. The introduction of continuous manufacturing lines for solid oral drug product has triggered increased interest in the application of such tools to determine the concentration of API in moving streams of powder. A key question in the development of such methods is the determination of an adequate frequency of sampling for the PAT devices, as it pertains the overall dynamics of the system

Our contribution will discuss a hybrid approach that uses information from a deterministic model, and the variability in the NIR spectra, along with time-series analysis techniques (such as ARX models, partial auto correlation coefficients, and cross-correlation coefficients) and the Shannon theorem of sampling to assess the adequacy of proposed frequencies of sampling and averaging in the spectrometer located in the feed-frame of the tablet press.