Badman C, Cooney CL, Florence A, Konstantinov K, Krumme M, Mascia S, et al. Why we need continuous pharmaceutical manufacturing and how to make it happen. J Pharm Sci. 2019;108(11):3521–3. https://doi.org/10.1016/j.xphs.2019.07.016.
Article CAS PubMed Google Scholar
Vanhoorne V, Vervaet C. Recent progress in continuous manufacturing of oral solid dosage forms. Int J Pharm. 2020;579:119194. https://doi.org/10.1016/j.ijpharm.2020.119194.
Article CAS PubMed Google Scholar
Lee SL, O’Connor TF, Yang X, Cruz CN, Chatterjee S, Madurawe RD, et al. Modernizing pharmaceutical manufacturing: from batch to continuous production. J Pharm Innov. 2015;10(3):191–9. https://doi.org/10.1007/s12247-015-9215-8.
Williams JC. Continuous mixing of solids. A review. Powder Technol. 1976;15(2):237–43. https://doi.org/10.1016/0032-5910(76)80052-6.
Gao Y, Vanarase A, Muzzio F, Ierapetritou M. Characterizing continuous powder mixing using residence time distribution. Chem Eng Sci. 2011;66(3):417–25. https://doi.org/10.1016/j.ces.2010.10.045.
Bautista M, Maurer R, Rolinger L, Gavi E. Piccione PM. Overview and control strategy insights. American Pharmaceutical Review: Mini-batch continuous direct compression; 2022. p. 1–8.
Karttunen AP, Poms J, Sacher S, Sparén A, Ruiz Samblás C, Fransson M, et al. Robustness of a continuous direct compression line against disturbances in feeding. Int J Pharm. 2020;574:118882. https://doi.org/10.1016/j.ijpharm.2019.118882.
Article CAS PubMed Google Scholar
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Continuous manufacturing of drug substances and drug products, Q13. In: ICH harmonised guideline. 2022. https://database.ich.org/sites/default/files/Q10%20Guideline.pdf. Accessed 24 Apr 2026.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Pharmaceutical quality system, Q10. In: ICH harmonized tripartite guideline. 2008. https://database.ich.org/sites/default/files/Q10%20Guideline.pdf. Accessed 24 Apr 2026.
Laske S, Paudel A, Scheibelhofer O, Sacher S, Hoermann T, Khinast J, et al. A review of PAT strategies in secondary solid oral dosage manufacturing of small molecules. J Pharm Sci. 2017;106(3):667–712. https://doi.org/10.1016/j.xphs.2016.11.011.
Article CAS PubMed Google Scholar
Almaya A, De Belder L, Meyer R, Nagapudi K, Lin H-R, Leavesley I, et al. Control strategies for drug product continuous direct compression—state of control, product collection strategies, and startup/shutdown operations for the production of clinical trial materials and commercial products. J Pharm Sci. 2017;106(4):930–43. https://doi.org/10.1016/j.xphs.2016.12.014.
Article CAS PubMed Google Scholar
Tantuccio ABA. Control strategy development for CM of OSD forms. In: ISPE good practice guide. 2025. https://ispe.org/publications/guidance-documents/good-practice-guide-control-strategy-development-cm-osd-forms. Accessed 24 Apr 2026.
Wang Y. Continuous Manufacturing: Commonly Asked Questions during Manufacturing Assessment. IFPAC Annual Meeting. N. Bethesda, MD, USA2022.
Kashinath KP, Sanjay LR, Ashokbhai MK, Roy S, Sardar MS, Kaity S. Continuous manufacturing based paradigm shift in pharmaceuticals production and current regulatory framework. Chem Eng Res Des. 2025;215:1–22. https://doi.org/10.1016/j.cherd.2025.01.003.
Harms ZD, Shi Z, Kulkarni RA, Myers DP. Characterization of near-infrared and Raman spectroscopy for in-line monitoring of a low-drug load formulation in a continuous manufacturing process. Anal Chem. 2019;91(13):8045–53. https://doi.org/10.1021/acs.analchem.8b05002.
Article CAS PubMed Google Scholar
Center for Drug Evaluation and Research, Food and Drug Administration. Considerations for complying with 21 CFR 211.110. In: Guidance for industry (draft). 2025. https://www.fda.gov/media/184825/download. Accessed 26 Apr 2026.
Meza CP, Santos MA, Romañach RJ. Quantitation of drug content in a low dosage formulation by transmission near infrared spectroscopy. AAPS PharmSciTech. 2006;7(1):E206–14. https://doi.org/10.1208/pt070129.
Doddridge GD, Shi Z. Multivariate figures of merit (FOM) investigation on the effect of instrument parameters on a Fourier transform-near infrared spectroscopy (FT-NIRS) based content uniformity method on core tablets. J Pharm Biomed Anal. 2015;102:535–43. https://doi.org/10.1016/j.jpba.2014.10.019.
Article CAS PubMed Google Scholar
Griffen JA, Owen AW, Matousek P. Quantifying low levels (<0.5% w/w) of warfarin sodium salts in oral solid dose forms using transmission Raman spectroscopy. J Pharm Biomed Anal. 2018;155:276–83. https://doi.org/10.1016/j.jpba.2018.04.008.
Article CAS PubMed Google Scholar
De Leersnyder F, Peeters E, Djalabi H, Vanhoorne V, Van Snick B, Hong K, et al. Development and validation of an in-line NIR spectroscopic method for continuous blend potency determination in the feed frame of a tablet press. J Pharm Biomed Anal. 2018;151:274–83. https://doi.org/10.1016/j.jpba.2018.01.032.
Article CAS PubMed Google Scholar
De Leersnyder F, Vanhoorne V, Kumar A, Vervaet C, De Beer T. Evaluation of an in-line NIR spectroscopic method for the determination of the residence time in a tablet press. Int J Pharm. 2019;565:358–66. https://doi.org/10.1016/j.ijpharm.2019.05.006.
Article CAS PubMed Google Scholar
Sierra-Vega NO, Martínez-Cartagena PA, Alvarado-Hernández BB, Romañach RJ, Méndez R. In-line monitoring of low drug concentration of flowing powders in a new sampler device. Int J Pharm. 2020;583:119358. https://doi.org/10.1016/j.ijpharm.2020.119358.
Article CAS PubMed Google Scholar
Ortega-Zúñiga C, la Rosa C-D, Román-Ospino AD, Serrano-Vargas A, Romañach RJ, Méndez R. Development of near infrared spectroscopic calibration models for in-line determination of low drug concentration, bulk density, and relative specific void volume within a feed frame. J Pharm Biomed Anal. 2019;164:211–22. https://doi.org/10.1016/j.jpba.2018.10.046.
Article CAS PubMed Google Scholar
Velez-Silva NL, Drennen JK 3rd, Anderson CA. Continuous manufacturing of pharmaceutical products: a density-insensitive near infrared method for the in-line monitoring of continuous powder streams. Int J Pharm. 2024;650:123699. https://doi.org/10.1016/j.ijpharm.2023.123699.
Sierra-Vega NO, Sánchez-Paternina A, Maldonado N, Cárdenas V, Romañach RJ, Méndez R. In line monitoring of the powder flow behavior and drug content in a Fette 3090 feed frame at different operating conditions using near infrared spectroscopy. J Pharm Biomed Anal. 2018;154:384–96. https://doi.org/10.1016/j.jpba.2018.03.017.
Article CAS PubMed Google Scholar
Sierra-Vega NO, Romañach RJ, Méndez R. Real-time quantification of low-dose cohesive formulations within a sampling interface for flowing powders. Int J Pharm. 2020. https://doi.org/10.1016/j.ijpharm.2020.119726.
Rangel-Gil RS, Sierra-Vega NO, Romañach RJ, Méndez R. Assessment of blend uniformity in a stream sampler device using Raman spectroscopy. Int J Pharm. 2023;639:122934. https://doi.org/10.1016/j.ijpharm.2023.122934.
Article CAS PubMed Google Scholar
Rangel-Gil RS, Nasrala-Álvarez JM, Romañach RJ, Méndez R. Blend uniformity monitoring in a continuous manufacturing mixing process for a low-dosage formulation using a stream sampler and near infrared spectroscopy. Int J Pharm. 2024;661:124478. https://doi.org/10.1016/j.ijpharm.2024.124478.
Article CAS PubMed Google Scholar
Román-Ospino AD, Baranwal Y, Li J, Vargas J, Igne B, Bate S, et al. Sampling optimization for blend monitoring of a low dose formulation in a tablet press feed frame using spatially resolved near-infrared spectroscopy. Int J Pharm. 2021;602:120594. https://doi.org/10.1016/j.ijpharm.2021.120594.
Article CAS PubMed Google Scholar
Mateo-Ortiz D, Colon Y, Romañach RJ, Méndez R. Analysis of powder phenomena inside a Fette 3090 feed frame using in-line NIR spectroscopy. J Pharm Biomed Anal. 2014;100:40–9. https://doi.org/10.1016/j.jpba.2014.07.014.
Article CAS PubMed Google Scholar
Ortega-Zúñiga CA, Román-Ospino AD, Gupta S, Omar T, Baranwal Y, Sanchez-Paternina A, et al. Real-time monitoring of small changes in powder blends and ejected tablets in a low-dose formulation with 1 %w/w of active pharmaceutical ingredient using Raman and near-infrared spatially resolved spectroscopy within a tablet press. Int J Pharm. 2025;670:125165. https://doi.org/10.1016/j.ijpharm.2025.125165.
Article CAS PubMed Google Scholar
De Man A, De Souter L, Shi Z, Mao C, De Beer T. Evaluating the improvement of blend potency measurements in the feed frame of a rotary tablet press using combined NIR and Raman spectroscopy. Anal Chem. 2024;96(26):10586–93. https://doi.org/10.1021/acs.analchem.4c01134.
Article CAS PubMed Google Scholar
Galata DL, Domokos A, Démuth B, Záhonyi P, Fülöp G, Nagy ZK, et al. In-line indirect concentration measurement of ultralow dose API during twin-screw wet granulation based on NIR and Raman spectroscopy. Int J Pharm. 2024;664:124650. https://doi.org/10.1016/j.ijpharm.2024.124650.
Comments (0)