Risk management for moisture related effects in dry manufacturing processes: a statistical approach

Abstract

A risk- and science-based approach to control the quality in pharmaceutical manufacturing includes a full understanding of how product attributes and process parameters relate to product performance through a proactive approach in formulation and process development. For dry manufacturing, where moisture content is not directly manipulated within the process, the variability in moisture of the incoming raw materials can impact both the processability and drug product quality attributes. A statistical approach is developed using individual raw material historical lots as a basis for the calculation of tolerance intervals for drug product moisture content so that risks associated with excursions in moisture content can be mitigated. The proposed method is based on a model-independent approach that uses available data to estimate parameters of interest that describe the population of blend moisture content values and which do not require knowledge of the individual blend moisture content values. Another advantage of the proposed tolerance intervals is that, it does not require the use of tabulated values for tolerance factors. This facilitates the implementation on any spreadsheet program like Microsoft Excel. A computational example is used to demonstrate the proposed method.

• Dry manufacturing
• effective sample size
• flowability
• moisture content
• satterthwaite approximation
• tablet compression
• tolerance interval

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.