The Role of Simulation and Scheduling Tools in the Development and Manufacturing of Active Pharmaceutical Ingredients

Petrides, Demetri; Koulouris, Alexandros; Siletti, Charles; Jiménez, José O.; Lagonikos, Pericles T.

doi:10.1002/9780470882221.ch28

Cited by 5 publications

(8 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To refer to literature and state of the art, the process was simulated with the database of a patent from SmithKline Beecham Corporation [81]. Missing parameters were added by other literature sources [17,71,72] and own knowledge/experience. The process flowsheet in Fig.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Process Development and Design of Downstream Processes

Strube¹,

Grote²,

Josch³

et al. 2011

Chemie Ingenieur Technik

View full text Add to dashboard Cite

State-of-the-art of process development, scale-up and design for downstream processes is described for complex mixtures in biotechnology. The focus is on fermentation broth and plant-based extracts to derive methodological arguments. Academic and industrial approaches are discussed with an assessment based on some process relevant criteria. Examples of monoclonal antibody, insulin and penicillin production processes are chosen to develop a sound argumentative basis.Demands of total process integration, accuracy and sensitivity of phenomena, resulting e.g. in miniaturization of laboratory experiments and linked with necessary in-depth modeling are developed and implemented. Specific tasks of unit operation are displayed and their integration into an efficient process sequence is demonstrated. Based on that, further research needs are pointed out and corresponding activities are identified. For instance, the transfer of well established methods in chemical engineering like process modeling in combination with laboratory scale experiments and final miniplant validation should be followed consequently also in biotechnology applications. Some drawbacks in academic education and industrial training as well as organizational structures are discussed to help address this issue.

show abstract

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Process Development and Design of Downstream Processes

Strube¹,

Grote²,

Josch³

et al. 2011

Chemie Ingenieur Technik

View full text Add to dashboard Cite

show abstract

“…A N U S C R I P T 5 stages of the drug production process (Azzaro-Pantel, 2018). Application of fundamental models for a variety of pharmaceutical processes has been discussed by several researchers (Benyahia et al, 2012;Gernaey and Gani, 2010;Hallow et al, 2010;Petrides et al, 2010Petrides et al, , 2002Poós and Szabó, 2017). For example, Hallow et al, (2010) developed a fundamental model to describe lactamization and ethanolysis reactions in a pharmaceutical production process (Hallow et al, 2010).…”

Section: A C C E P T E D Mmentioning

confidence: 99%

Sequential model-based A- and V-optimal design of experiments for building fundamental models of pharmaceutical production processes

Shahmohammadi

McAuley

2019

Computers & Chemical Engineering

View full text Add to dashboard Cite

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights Sequential model-based design of experiments results in informative experimental data for estimating parameters and making predictions using fundamental models.  Inversion of Fisher Information Matrix (FIM) is required for model-based design of experiments. The FIM may be noninvertible for complex chemical and pharmacological process models. Parameter subset selection leaves out problematic parameters, resulting in a reduced FIM that is effective for experimental design.

show abstract

“…Those techniques include centrifugation (Hu et al, 2017), distillation (Joglekar et al, 2006), extraction (Khunnonkwao et al, 2012), crystallization (Tait et al, 2009), evaporation (Petrides et al, 2002), adsorption (ion exchanger) including membrane filtration (microfiltration (MF), ultrafiltration (UF), nanofiltration (NF), reverse osmosis (RO) and electrodialysis (ED) (Rodrigues et al, 2017).…”

Section: List Of Figuresmentioning

confidence: 99%

“…Many process simulation tools have been continuously applied in chemical industries for developing and optimizing the design and operation of integrated process since 1960s. When a new process model is proposed, process simulators can generate the model that predicts the equipment sizing, process scheduling, and economic evaluation (Petrides et al, 2002). Thus, the simulation results are often used as one of the tools to guarantee the process feasibility at the initial stage of development.…”

Section: List Of Figuresmentioning

confidence: 99%

“…Process simulation tools have been continuously applied in petrochemical industries for developing and optimizing the design and operation of integrated processes since 1960s. When a new process scale is required, process simulators can be used to model the required equipment size as well as to estimate the cost of equipment (Petrides et al, 2002). Various software tools were performed such as bioprocess simulator (BPS), Biopro Designer, Superpro designer, biotechnology design simulator (BDS) and batch process technology (BATCHES).…”

Section: Process Simulationmentioning

confidence: 99%

See 1 more Smart Citation

Separation and purification of lactic acid from fermentation broth by reverse osmosis

Phanthumchinda

View full text Add to dashboard Cite

Brackish water reverse osmosis (BWRO) and seawater reverse osmosis (SWRO) membranes were used in the 2-stage reverse osmosis (RO) unit to recover, pre-purify, and pre-concentrate lactic acid. Calcium lactate (CaLAC), sodium lactate (NaLAC), and ammonium lactate (NH4LAC) were used as model feed solutions. The operating pressure showed a pronounced effect on lactate passage through the first BWRO unit, and the Donnan exclusion effect and hydrogen bonding were responsible for cation rejection. Calcium ions were rejected at the BWRO unit because of low diffusion rate and charge interaction at the surface. However, monovalent ions formed hydrogen bonds with the carbonyl group of the membrane that allowed passage across the membrane. The second SWRO unit was for pre-concentrating lactic acid. A high lactate purity of 99.2% with a total recovery of 50.5% was acquired from calcium lactate feed solution. Lower purity with higher lactate recovery was obtained when the feed solution was sodium lactate and ammonium lactate. Process and cost models for lactic acid recovery from fermentation broths at an annual capacity of 100,000 kg were developed as a research tool in evaluating an alternated process technology. The models were developed using SuperPro? Designer software by gathering the optimized data from the laboratory scale experiments. Sizing of unit operations, chemicals and utility consumptions, and estimation of capital and operating costs with the cost breakdown analysis were acquired from the simulation. Membrane based process design was proposed in this study. The processes mainly consisted of microfiltration for cell removal, a series of ultrafiltration for eliminating proteins, and the integrated reverse osmosis systems to recover, preconcentrate, and prepurify lactic acid. Among the 3 proposed process designs, in-parallel membrane based process exhibited the highest lactic acid recovery yield while the purity remained sufficiently high in comparable to the commercial grade products. The number of unit operations was found to be responsible to high production cost both investment and operating costs. Omitting centrifugation and ultrafiltration at 30 kDa molecular weight cut-off with integrated brackish water reverse osmosis membrane in parallel units in the design could lower the operating cost by 23.33-31.29% for different fermentation broths entering the downstream processing units.

show abstract

The Role of Simulation and Scheduling Tools in the Development and Manufacturing of Active Pharmaceutical Ingredients

Cited by 5 publications

References 3 publications

Process Development and Design of Downstream Processes

Process Development and Design of Downstream Processes

Sequential model-based A- and V-optimal design of experiments for building fundamental models of pharmaceutical production processes

Separation and purification of lactic acid from fermentation broth by reverse osmosis

Contact Info

Product

Resources

About