Real-Time Release Testing of Herbal Extract Powder by Near-Infrared Spectroscopy considering the Uncertainty around Specification Limits

Abstract

The concept of real-time release testing (RTRT) has recently been adopted by the production of pharmaceuticals in order to provide high-level guarantee of product quality. Process analytical technology (PAT) is an attractive and efficient way for realizing RTRT. In this paper, near-infrared (NIR) determination of cryptotanshinone and tanshinoneIIA content in tanshinone extract powders was taken as the research object. The aim of NIR analysis is to reliably declare the extract product as compliant with its specification limits or not. First, the NIR quantification method was developed and the parameters of the multivariate calibration model were optimized. The reliable concentration ranges covering the specification limits of two APIs were successfully verified by the accuracy profile (AP) methodology. Then, with the designed validation data from AP, the unreliability graph as the decision tool was built. Innovatively, the β-content, γ-confidence tolerance intervals (β-CTIs) around the specification limits were estimated. During routine use, the boundary of β-CTIs could help decide whether the NIR prediction results are acceptable. The proposed method quantified the analysis risk near the specification limits and confirmed that the unreliable region was useful to release the product quality in a real-time way. Such release strategy could be extended for other PAT applications to improve the reliability of results.

Towards real time release testing of Shuxuening injection based on near infrared spectroscopy and accuracy profile

“…34 The unreliability regions close to the specification limits can be recognized to enable better risk management and provide a more reliable release. [35][36][37] Thus, it also complies with the ICH Q9 guidance. 38 In the present study, the aim was first to develop a robust NIR model to determine the content of active ingredients in SXNI.…”

“…34 The unreliability regions close to the specification limits can be recognized to enable better risk management and provide a more reliable release. 35-37 Thus, it also complies with the ICH Q9 guidance. 38…”

Trends in digital detection for the quality and safety of herbs using infrared and Raman spectroscopy

“…They regarded water as a probe to understand better and visualize the extraction process. The unreliability graph methodology was innovatively proposed as a release strategy in tanshinone extract powders after the establishment of NIRS-PLS model ( Shi et al., 2019 ).…”