Design and Commercialization of an End-to-End Continuous Pharmaceutical Production Process: A Pilot Plant Case Study

TLDR

The pharmaceutical industry’s batch‑wise manufacturing creates inefficiencies, quality‑control issues, and supply‑chain vulnerabilities, prompting growing interest in continuous processes supported by regulatory encouragement and technological advances. This study presents a quality‑by‑design strategy and operation of an end‑to‑end integrated continuous manufacturing pilot plant that produces both small‑molecule API and oral solid dosages, while addressing quality and economic considerations for scale‑up and commercialization. The authors implemented a QbD‑based design approach to develop and operate the pilot plant, integrating continuous processes for API synthesis and tablet formulation into a single end‑to‑end production line. The integrated continuous manufacturing pilot plant achieved significant benefits, including improved quality control, enhanced supply‑chain flexibility, a ~90% reduction in capital investment, and operating‑cost reductions of 33.6% for API and 29.4% for tablets.

Abstract

The pharmaceutical industry faces multiple challenges (e.g., inefficient manufacturing techniques, quality control issues, and supply chain vulnerabilities) because of its current batch-wise approach to manufacturing. Recent regulatory support for continuous manufacturing and advances in continuous process technologies have caused an increase in interest from some drug manufacturers to modernize their production processes. However, many of these companies have focused on hybrid processes, where only certain steps are continuous, while others remain batch. Herein, the quality by design (QbD)-based design strategy and operation of an end-to-end integrated continuous manufacturing (ICM) pilot plant that produces both small-molecule active pharmaceutical ingredient (API) and oral solid dosages (OSDs) are discussed. Additionally, important quality and economic matters pertaining to scale-up and commercialization are addressed. ICM has significant benefits, including better quality control, increased supply chain flexibility, a lower capital investment (in the example provided, a ∼ 90% reduction), and lower operating costs (in the example provided, a 33.6% reduction for API and 29.4% reduction for tablets).