Background/Objectives: Quality by Design (QbD) has revolutionized pharmaceutical development by transitioning from reactive quality testing to proactive, science-driven methodologies. Rooted in ICH Q8–Q11 guidelines, QbD emphasizes defining Critical Quality Attributes (CQAs), establishing design spaces, and integrating risk management to enhance product robustness and regulatory flexibility. This review critically examines QbD’s theoretical frameworks, implementation workflows, and industrial applications, aiming to bridge academic research and commercial practices while addressing emerging challenges in biologics, advanced therapies, and personalized medicine. Methods: The review synthesizes regulatory guidelines, case studies, and multidisciplinary tools, including Design of Experiments (DoE), Failure Mode Effects Analysis (FMEA), Process Analytical Technology (PAT), and multivariate modeling. It evaluates QbD workflows—from Quality Target Product Profile (QTPP) definition to control strategies—and explores advanced technologies like AI-driven predictive modeling, digital twins, and continuous manufacturing. Results: QbD implementation reduces batch failures by 40%, optimizes dissolution profiles, and enhances process robustness through real-time monitoring (PAT) and adaptive control. However, technical barriers, such as nonlinear parameter interactions in complex systems, and regulatory disparities between agencies hinder broader adoption. Conclusions: QbD significantly advances pharmaceutical quality and efficiency, yet requires harmonized regulatory standards, lifecycle validation protocols, and cultural shifts toward interdisciplinary collaboration. Emerging trends, including AI-integrated design space exploration and 3D-printed personalized medicines, promise to address scalability and patient-centric needs. By fostering innovation and compliance, QbD remains pivotal in achieving sustainable, patient-focused drug development.

Chemical sensors are powerful for the fast recognition of chiral compounds. However, the established sensing systems are less effective for chiral tertiary alcohols. The chiral tertiary alcohol group is an important structural unit in natural products and drug molecules, and its enantioselective recognition represents a significant and challenging task. In this paper, a novel type of chiral bisselenourea sensor was first synthesized and used as a strong hydrogen-bonding donor for highly efficient chiral recognition of a diverse range of tertiary alcohols. The obtained sharply split NMR signals are well-distinguishable with a large (up to 0.415 ppm) chemical shift nonequivalence. The NMR signal of the hydroxyl hydrogen atom was first employed for enantiomeric excess determination of tertiary alcohols, giving accurate results with <2% absolute errors. The 2D NOESY spectra and computational studies suggest that the geometrical differentiation of the formed diastereomeric complexes between the sensor and tertiary alcohols enables the chiral discrimination of the hydroxyl hydrogen signals of the tertiary alcohol in the ¹H NMR spectrum.

In this work, a novel method for assigning the absolute configuration of a chiral primary amine has been developed based on the experimental and DFT-calculated ¹⁹F NMR chemical shift differences of its derived two fluorinated amides by reacting with two enantiomers of a chiral derivatizing agent FPP (α-fluorinated phenylacetic phenylselenoester) separately. Comparing the experimental chemical shift difference $\Delta {\delta }_{\alpha -F}^{R,S}$ of (R)-FPA-amide/(S)-FPA-amide with the calculated Δδ_α-F^R,S of (R)-FPA-(R)-amide/(S)-FPA-(R)-amide, if the experimental Δδ_α-F^R,S has the same symbol (positive or negative) as one of the theoretical Δδ_α-F^R,S, the assigned configuration of the amine is considered to be consistent with the theoretical one. Our method could be applied to a broad substrate scope avoiding wrong conclusion due to empirical judgment.

An approach to chiral quaternary 3-aminooxindoles via Et ₂ Zn catalyzed diastereoselective addition of various Grignard reagents to broad isaltin-derived N-tert -butanesulfinyl ketimines promoted by zinc( ii ) chloride.