Mitigating the Risks of Generic Drug Product Development: An Application of Quality by Design (QbD) and Question based Review (QbR) Approaches

摘要

This paper discusses the challenges and opportunities of implementing the Quality by Design (QbD) and Question based Review (QbR) approaches in developing solid dosage formulations and manufacturing processes for generic drug products. Formulation and process development of a drug product is a challenge due to the inherent variability associated with the activity. Regulatory bodies, such as the Food and Drug Administration (FDA) of the USA, require the QbD approach in developing formulations and processes for drug products. The QbD approach is described in the International Conference on Harmonisation (ICH) guidance Q8 (R2). The regulatory reviewers follow the QbR approach during the review of Chemistry, Manufacturing, and Controls (CMC), which have also adopted some of the elements of the QbD guidance. A systematic application of scientific principles in developing the formulations and processes for generic drug products following the QbD approach is outlined in three main categories. The categories are (A) product understanding, (B) process understanding, and (C) control strategy. The concept of predefined objectives, quality risk management, and CMC considerations along with the prior knowledge are discussed in details. The discussions and explanations provided in this paper are based on sound scientific principles as well as practical experience and approaches applied to resolve product quality and manufacturing issues. Emphasis is given to streamlining the formulations and process development activity to comply with the QbD and QbR principles and to avoid commonly cited deficiencies. The examples are provided as guiding tools for the generic formulation and process development professionals.