scholarly journals Combining Mechanistic Modeling and Raman Spectroscopy for Monitoring Antibody Chromatographic Purification

Processes ◽  
2019 ◽  
Vol 7 (10) ◽  
pp. 683 ◽  
Author(s):  
Feidl ◽  
Garbellini ◽  
Luna ◽  
Vogg ◽  
Souquet ◽  
...  

Chromatography is widely used in biotherapeutics manufacturing, and the corresponding underlying mechanisms are well understood. To enable process control and automation, spectroscopic techniques are very convenient as on-line sensors, but their application is often limited by their sensitivity. In this work, we investigate the implementation of Raman spectroscopy to monitor monoclonal antibody (mAb) breakthrough (BT) curves in chromatographic operations with a low titer harvest. A state estimation procedure is developed by combining information coming from a lumped kinetic model (LKM) and a Raman analyzer in the frame of an extended Kalman filter approach (EKF). A comparison with suitable experimental data shows that this approach allows for the obtainment of reliable estimates of antibody concentrations with reduced noise and increased robustness.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 475
Author(s):  
Guijin Liu ◽  
Junjian Li ◽  
Shiming Deng

Solid multicomponent systems (SMS) are gaining an increasingly important role in the pharmaceutical industry, to improve the physicochemical properties of active pharmaceutical ingredients (APIs). In recent years, various processes have been employed for SMS manufacturing. Control of the particle solid-state properties, such as size, morphology, and crystal form is required to optimize the SMS formulation. By utilizing the unique and tunable properties of supercritical fluids, supercritical anti-solvent (SAS) process holds great promise for the manipulation of the solid-state properties of APIs. The SAS techniques have been developed from batch to continuous mode. Their applications in SMS preparation are summarized in this review. Many pharmaceutical co-crystals and solid dispersions have been successfully produced via the SAS process, where the solid-state properties of APIs can be well designed by controlling the operating parameters. The underlying mechanisms on the manipulation of solid-state properties are discussed, with the help of on-line monitoring and computational techniques. With continuous researching, SAS process will give a large contribution to the scalable and continuous manufacturing of desired SMS in the near future.


2003 ◽  
Vol 75 (9) ◽  
pp. 2166-2171 ◽  
Author(s):  
Nicolae Leopold ◽  
Michael Haberkorn ◽  
Thomas Laurell ◽  
Johan Nilsson ◽  
Josefa R. Baena ◽  
...  

2009 ◽  
Vol 49 (11) ◽  
pp. 2125-2131 ◽  
Author(s):  
Miguel A. Corona-Rivera ◽  
Jorge Flores ◽  
Jorge E. Puig ◽  
Eduardo Mendizábal

2008 ◽  
Vol 4 (T27A) ◽  
pp. 375-384
Author(s):  
Gillian Nave ◽  
Glenn M. Wahlgren ◽  
Jeffrey R. Fuhr

The references cited in this section are mostly papers on original laboratory research; compilations and data bases are covered in another section. The references, ordered by atomic number and spectrum, are given in parentheses following the spectral notations. References including experimental data on line structure, hyperfine structure (HFS) or isotope structure (IS) are also included.


2012 ◽  
Vol 11 (4) ◽  
pp. 269-278 ◽  
Author(s):  
Howell G.M. Edwards ◽  
Ian B. Hutchinson ◽  
Richard Ingley

AbstractThe survival strategies of extremophilic organisms in terrestrially stressed locations and habitats are critically dependent on the production of protective chemicals in response to desiccation, low wavelength radiation insolation, temperature and the availability of nutrients. The adaptation of life to these harsh prevailing conditions involves the control of the substratal geology; the interaction between the rock and the organisms is critical and the biological modification of the geological matrix plays a very significant role in the overall survival strategy. Identification of these biological and biogeological chemical molecular signatures in the geological record is necessary for the recognition of the presence of extinct or extant life in terrestrial and extraterrestrial scenarios. Raman spectroscopic techniques have been identified as valuable instrumentation for the detection of life extra-terrestrially because of the use of non-invasive laser-based excitation of organic and inorganic molecules, and molecular ions with high discrimination characteristics; the interactions effected between biological organisms and their environments are detectable through the molecular entities produced at the interfaces, for which the vibrational spectroscopic band signatures are unique. A very important attribute of Raman spectroscopy is the acquisition of molecular experimental data non-destructively without the need for chemical or mechanical pre-treatment of the specimen; this has been a major factor in the proposal for the adoption of Raman instrumentation on robotic landers and rovers for planetary exploration, particularly for the forthcoming European Space Agency (ESA)/National Aeronautics and Space Administration (NASA) ExoMars mission. In this paper, the merits of using Raman spectroscopy for the recognition of key molecular biosignatures from several terrestrial extremophile specimens will be illustrated. The data and specimens used in this presentation have been acquired from Arctic and Antarctic cold deserts and a meteorite crater, from which it will be possible to assess spectral data relevant for the detection of extra-terrestrial extremophilic life signatures.


2002 ◽  
Vol 45 (6) ◽  
pp. 41-49 ◽  
Author(s):  
I. Nopens ◽  
C.A. Biggs ◽  
B. De Clercq ◽  
R. Govoreanu ◽  
B.-M. Wilén ◽  
...  

A technique based on laser light diffraction is shown to be successful in collecting on-line experimental data. Time series of floc size distributions (FSD) under different shear rates (G) and calcium additions were collected. The steady state mass mean diameter decreased with increasing shear rate G and increased when calcium additions exceeded 8 mg/l. A so-called population balance model (PBM) was used to describe the experimental data. This kind of model describes both aggregation and breakage through birth and death terms. A discretised PBM was used since analytical solutions of the integro-partial differential equations are non-existing. Despite the complexity of the model, only 2 parameters need to be estimated: the aggregation rate and the breakage rate. The model seems, however, to lack flexibility. Also, the description of the floc size distribution (FSD) in time is not accurate.


2021 ◽  
Author(s):  
Sarah Klingler ◽  
Julian Hniopek ◽  
Robert Stach ◽  
Michael Schmitt ◽  
Jürgen Popp ◽  
...  

Scientific questions in fields such as catalysis, monitoring of biological processes or environmental chemistry demand for analytical technologies combining orthogonal spectroscopies. Combined spectroscopic concepts facilitate in-situ on-line monitoring of dynamic processes providing for a better understanding of the involved reaction pathways. In the present study, a low-liquid-volume multi-spectroscopic platform was developed based on infrared attenuated total reflection (IR-ATR) spectroscopy combined with Raman spectroscopy and lumines-cence sensing. For demonstrating the measurement capabilities, exemplary analyte systems including water / heavy water and aqueous solutions of ammonium sulfate were analyzed as proof-of-principle studies. It was successfully demonstrated that three optical techniques may be integrated into a single analytical platform with-out interference providing synchronized and complementary datasets by probing the same minute sample vol-ume. In addition, the developed assembly provides a gas-tight lid sealing the headspace above the probed liq-uid for monitoring the concentration of molecular oxygen also in the gas phase via luminescence quenching. Hence, the entire assembly may be operated at inert conditions, as required for example during the analysis of photocatalytic processes.


2018 ◽  
Author(s):  
Malgorzata Zawadzka ◽  
Beatrix Ràcz ◽  
Dario Ambrosini ◽  
Carl Henrik Gørbitz ◽  
Jens Preben Morth ◽  
...  

AbstractAn ultraviolet (UV)-absorbing compound of unknown identity is present in the aqueous humor of geese and other birds flying at high altitudes. A goose aqueous humor extract, that was believed to contain the UV protective compound which was designated as “compound X”, was fractionated and examined using a variety of spectroscopic techniques including LC-MS and high field one- and two dimensional-NMR methods. A series of compounds were identified but none of them appeared to be the UV protective “compound X”. It may be that the level of the UV protective compound in goose aqueous humor is much less than the compounds identified in our investigation, or it may have been degraded by the isolation and chromatographic purification protocols used in our investigations.


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