13/14 March 2024
Near infrared (NIR) analytical procedures are widely used in the pharmaceutical industry for identification testing and assay measurements performed on pharmaceutical starting materials, intermediates, and finished products, and for monitoring and controlling manufacturing processes. In this context, the U.S. Food and Drug Administration (FDA) has published a new Guidance for Industry entitled Development and Submission of Near Infrared Analytical Procedures.
According to the FDA, "the guidance provides recommendations to applicants to aid the development, validation, and use of near infrared (NIR)-based analytical procedures in evaluating the identity, strength, quality, purity, and potency of drug substances and drug products. The recommendations apply to new drug applications (NDAs), abbreviated new drug applications (ANDAs), and supplemental NDAs and ANDAs for small molecule drugs. The principles in this guidance also apply to drug substances and drug products covered in Type II drug master files." It is noted that the document "pertains only to the development and validation of NIR analytical procedures and does not provide recommendations concerning the setup, qualification, maintenance, or calibration of NIR instruments."
The 25-page document is divided into an introduction, a description of the background, six main chapters (Chapter III., IV., V., VI., VII., and VIII.), and a glossary.
The PDF document of the final guidance is available on the FDA's website.
Chapter III. of the document deals with modes of measurement commonly used for process understanding, monitoring, and control:
In this regard, the guidance describes some specific features that applicants should consider during development when selecting the appropriate mode of measurement for NIR implementation.
The following chapter (Chapter IV.) names and explains the steps that the development of a NIR model should include:
In Chapter V., it is pointed out that "applicants should perform validation after their chemometric models are developed. This validation is sometimes referred to as external validation. Internal validation of the chemometric model is not considered a substitute for external validation."
These introductory remarks are followed by explanations of how qualitative analytical, quantitative analytical, and rate-of-change procedures should be validated.
As a general rule, "applicants must ensure that NIR analytical procedures are appropriately followed, maintained, and updated as needed throughout the drug product's life cycle in accordance with CGMP requirements." According to the information given in Chapter VI., this requires that drug product manufacturers establish procedures to
For NIR analytical procedures, applicants should provide information concerning
Chapter VII. of the guidance also lists which information should be provided for the development of NIR analytical procedures concerning
For the validation of NIR analytical procedures, FDA expects at least the following information:
Chapter VIII. finally provides recommendations for the life cycle management, especially of how the potential impact of a change to the NIR procedure and the appropriate corresponding reporting mechanism can be evaluated.
A distinction is made between the following types of postapproval changes: