The US Food and Drug Administration (FDA) has issued draft guidance to provide recommendations to applicants of new drug applications (NDAs), abbreviated new drug applications (ANDAs), and drug master file (DMF) holders regarding the development and submission of near infrared (NIR) analytical procedures used during the manufacture and analysis of pharmaceuticals (including raw materials, in-process materials and intermediates, and finished products). It also provides recommendations regarding how the concepts described in the International Conference on Harmonization (ICH) guidance for industry Q2(R1) Validation of Analytical Procedures: Text and Methodology (ICH Q2(R1)) and PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance can be applied to the development, validation, and submission of NIR analytical procedures.
This guidance only pertains to the development and validation of NIR analytical procedures and does not provide recommendations concerning the set-up and qualification of NIR instruments or their maintenance and calibration. While this guidance is written specifically for NIR, the fundamental concepts of validation can be applied to other PAT technologies including Raman, focused beam reflection measurement, particle imaging, and X-ray, among other techniques.
NIR analytical procedures are increasingly being used in the pharmaceutical industry for the identification and assay of pharmaceutical starting materials, intermediates, and finished products. They are also used to monitor and control manufacturing processes. The development and validation of NIR analytical procedures are therefore important for ensuring the quality of pharmaceuticals. In issuing the draft guidance, the FDA said it is important for manufacturers who use such procedures to understand the factors that can affect the performance and suitability of the procedures and the approaches that can be used to validate them.
NIR analytical procedures typically combine the following: (1) elements of instrumentation (analyzer consisting of a NIR spectrophotometer, reflectance or transmission probe, spectral analysis software, etc.), (2) acquisition parameters, (3) sample presentation (interface) and sampling, (4) composition of spectral data sets, (5) spectral pretreatment, (6) wavelength range(s), and (7) a chemometric model, and can therefore be considered more complicated than the types of analytical procedures for which ICH Q2(R1) was written. This guidance is intended to discuss how the concepts described in ICH Q2(R1) can be applied to NIR analytical procedures that use chemometric models and to describe the FDA's Center for Drug Evaluation and Research's current thinking about other issues related to the development and validation of NIR analytical procedures. This draft guidance is also intended to describe the type of information that should be submitted about NIR analytical procedures in applications.