The document outlines an approach to developing a robust process for producing a crystalline form of a drug using mechanistic understanding rather than statistical modeling alone. Key factors like temperature, solvent composition, and water content were identified through solubility studies and reaction monitoring, allowing a targeted design of experiments. The initial process worked well at scale but later required modification when a new solvate form appeared. Repeating the mechanistic work incorporating prior knowledge improved the process design and mitigated issues with particle size and form variability.
Typical shelf life testing takes months to perform. Manufacturers must test for each mode of failure and then model product changes at different temperatures and water activities to predict optimal shelf life conditions. But what if you could test and model all modes of failure at the same time?
Quality Control Analysis of Natural Gas Condensate Products through Refining Process
Sarker, K., Faruque, M.O. (2017).Quality Control Analysis of Natural Gas Condensate Products through Refining Process.In International Conference on Engineering, Research, Innovation and Education.Shahjalal University of Science and Technology, Sylhet, Bangladesh, January 13-15. Sylhet, Bangladesh: School of Applied Sciences and Technology. 529-534.
Typical shelf life testing takes months to perform. Manufacturers must test for each mode of failure and then model product changes at different temperatures and water activities to predict optimal shelf life conditions. But what if you could test and model all modes of failure at the same time?
Quality Control Analysis of Natural Gas Condensate Products through Refining Process
Sarker, K., Faruque, M.O. (2017).Quality Control Analysis of Natural Gas Condensate Products through Refining Process.In International Conference on Engineering, Research, Innovation and Education.Shahjalal University of Science and Technology, Sylhet, Bangladesh, January 13-15. Sylhet, Bangladesh: School of Applied Sciences and Technology. 529-534.
Call it baking, smoking, curing, dehydrating, or drying, the vast majority of food processors have to remove water from food. Optimizing your process can deliver significant yield increases—often more than 3%.
In this 30 minute webinar, Scott Campbell shares key insights that will help you achieve significant gains, including:
• modern methods for reducing the most challenging sources of variation
• higher-accuracy measurements that allow tighter specifications
the role of extrinsic and intrinsic variables in evaluating yield, quality, and safety
• how—and why—to characterize your drying process
Watch the webinar:
https://www.metergroup.com/food/events/drying-mistakes-that-kill-your-yield/
Development and Scale Up Of a Chemical Process in Pharmaceutical Industry: A ...IJERA Editor
Every process has its own significance and one has to study factors which impact to the process and its
procedure to be followed. This paper is more concerned of how a process is scaled up from lab scale to pilot
plant scale, which is the major step in any industry because moving directly towards manufacturing level
consumes time and money. The report introduces about pharmaceutical industry and how it is different from
the other industries and provides firsthand experience for all the engineers to explore the equipment, process
and unit operations included in it. First aspect of scale up is safety and then comes economy, purity and
optimums. It includes the process and its unit operations such as reactors, distillation, filtration,
crystallization, drying and the equipment involving these operations. Consequently, the scale up rules,
factors influenced strategies and other considerations are observed. To learn and understand the unit process
and operations with their importance, a case study taking one of the stages of production is discussed here.
Optimizing the Reverse Osmosis Process Parameters by Maximizing Recovery by T...QUESTJOURNAL
ABSTRACT: In this study, the effects of Operating Pressure, Potential Hydrogen, Oxidation Reduction Potential and Anti Scaling Agent on multi responses like Permeate, COD, Total Solids, Conductivity and Hardness in the Reverse Osmosis Process were experimentally investigated on RO 8100 ST8 PT44 400Wl machine. The settings of RO parameters were determined by using Taguchi’s experimental design method. Orthogonal arrays of Taguchi, the signal-to-noise (S/N) ratio, the analysis of variance (ANOVA) are employed to find the optimal levels and to analyze the effect of the RO parameters. Results show that potential of hydrogen, operating pressure, oxidation reduction potential and anti scaling agent are the four Parameters that influence the Permit more effectively and COD, Total Solids, Conductivity and Hardness respectively. Improvement in recovery of RO process is achieved with optimize setting. Finally, the ranges for best RO conditions are proposed for ZLD process.
Validation is the process of checking of the process, equipment and method whereas qualification is solely done for equipment and qualification of instrument helps in quality of pharmaceutical product.
Call it baking, smoking, curing, dehydrating, or drying, the vast majority of food processors have to remove water from food. Optimizing your process can deliver significant yield increases—often more than 3%.
In this 30 minute webinar, Scott Campbell shares key insights that will help you achieve significant gains, including:
• modern methods for reducing the most challenging sources of variation
• higher-accuracy measurements that allow tighter specifications
the role of extrinsic and intrinsic variables in evaluating yield, quality, and safety
• how—and why—to characterize your drying process
Watch the webinar:
https://www.metergroup.com/food/events/drying-mistakes-that-kill-your-yield/
Development and Scale Up Of a Chemical Process in Pharmaceutical Industry: A ...IJERA Editor
Every process has its own significance and one has to study factors which impact to the process and its
procedure to be followed. This paper is more concerned of how a process is scaled up from lab scale to pilot
plant scale, which is the major step in any industry because moving directly towards manufacturing level
consumes time and money. The report introduces about pharmaceutical industry and how it is different from
the other industries and provides firsthand experience for all the engineers to explore the equipment, process
and unit operations included in it. First aspect of scale up is safety and then comes economy, purity and
optimums. It includes the process and its unit operations such as reactors, distillation, filtration,
crystallization, drying and the equipment involving these operations. Consequently, the scale up rules,
factors influenced strategies and other considerations are observed. To learn and understand the unit process
and operations with their importance, a case study taking one of the stages of production is discussed here.
Optimizing the Reverse Osmosis Process Parameters by Maximizing Recovery by T...QUESTJOURNAL
ABSTRACT: In this study, the effects of Operating Pressure, Potential Hydrogen, Oxidation Reduction Potential and Anti Scaling Agent on multi responses like Permeate, COD, Total Solids, Conductivity and Hardness in the Reverse Osmosis Process were experimentally investigated on RO 8100 ST8 PT44 400Wl machine. The settings of RO parameters were determined by using Taguchi’s experimental design method. Orthogonal arrays of Taguchi, the signal-to-noise (S/N) ratio, the analysis of variance (ANOVA) are employed to find the optimal levels and to analyze the effect of the RO parameters. Results show that potential of hydrogen, operating pressure, oxidation reduction potential and anti scaling agent are the four Parameters that influence the Permit more effectively and COD, Total Solids, Conductivity and Hardness respectively. Improvement in recovery of RO process is achieved with optimize setting. Finally, the ranges for best RO conditions are proposed for ZLD process.
Validation is the process of checking of the process, equipment and method whereas qualification is solely done for equipment and qualification of instrument helps in quality of pharmaceutical product.
Advances in Organic Chemistry in Academia Using Real-Time In Situ Mid-FTIR - ...pscholl
Three case studies from scientific literature that illustrate how real-time in situ mid-FTIR (ReactIR) is used to advance the understanding of chemical reactions. Email me at paul.scholl@mt.com if you are interested in links to technical webinars and whitepapers on the topics of mid-FTIR in situ reaction analysis, process characterization & scale-up and reaction calorimetry.
CRI/Criterion has deployed high-throughput tools for formulation of new catalyst compositions, and for testing the performance of the catalysts in several applications. This ability allows for screening of a large number of catalysts in a very short amount of time, significantly reducing the time required for catalyst development. The high-throughput screening ability has been proven in several areas of CRI/Criterion’s businesses, including chemicals and refining. High-throughput screening tools are equally, if not more, valuable in speedy deployment of biofuels and biochemicals from the lab to the market. Here we provide an overview of a program for rapid catalyst and process development to convert a mixed alcohol feed into gasoline and kerosene range hydrocarbons.
Fast-track solutions to address challenges with Host Cell Proteins in early d...Merck Life Sciences
Watch this webinar here: https://bit.ly/3fFRXDb
This webinar illustrates a customer case study about the challenges related to the removal of Host Cell Proteins from bioreactor harvest, the selected fast-track approach and outcome.
Our customer had one month to reduce the level of HCPs in the bioreactor harvest prior to a production run to supply drug substance for a scheduled Phase 1 clinical trial. The high level of HCPs (1,000,000 in the harvest and 700 ppm at the end of purification) unfavorably impacted the planned clarification process and subsequent downstream steps.
The goal was to reduce the level of HCPs to maximum of 300 ppm at the end of process purification and ensure clarification of the entire 2000L harvest.
In this webinar, you will learn about:
- Challenges with Host Cell Proteins
- Fast-Track Approach using caprylic acid precipitation followed by filtration using Clarisolve® filters
- The impact of Design of Experiment
Fast-track solutions to address challenges with Host Cell Proteins in early d...MilliporeSigma
Watch this webinar here: https://bit.ly/3fFRXDb
This webinar illustrates a customer case study about the challenges related to the removal of Host Cell Proteins from bioreactor harvest, the selected fast-track approach and outcome.
Our customer had one month to reduce the level of HCPs in the bioreactor harvest prior to a production run to supply drug substance for a scheduled Phase 1 clinical trial. The high level of HCPs (1,000,000 in the harvest and 700 ppm at the end of purification) unfavorably impacted the planned clarification process and subsequent downstream steps.
The goal was to reduce the level of HCPs to maximum of 300 ppm at the end of process purification and ensure clarification of the entire 2000L harvest.
In this webinar, you will learn about:
- Challenges with Host Cell Proteins
- Fast-Track Approach using caprylic acid precipitation followed by filtration using Clarisolve® filters
- The impact of Design of Experiment
Episode 55 : Conceptual Process Synthesis-Design
Process Flowsheet Synthesis: Method to determine a process flowsheet that satisfies all product, operational and other requirements
SAJJAD KHUDHUR ABBAS
Ceo , Founder & Head of SHacademy
Chemical Engineering , Al-Muthanna University, Iraq
Oil & Gas Safety and Health Professional – OSHACADEMY
Trainer of Trainers (TOT) - Canadian Center of Human
Development
Understanding Isotherms: What vapor sorption can and can’t tell youMETER Group, Inc. USA
Moisture content and water activity. Each has its assigned roles and responsibilities. They’re often used separately, and for very different purposes. But can they work together?
In this live webinar, our METER experts will break down how and why mapping moisture content and water activity together – and how they change over time – can open a new world of valuable information.
You’ll learn:
— Why MC and aW combined can tell you more than they would separately
— All the ways to create isotherms, plus the strengths and weaknesses of each method
— How to interpret and use your moisture sorption isotherms
— Why isotherms can predict texture changes so precisely
— Why shelf life and packaging decisions can be made faster using isotherms
— How to extract business value from your isotherms – both in and out of the R&D department
Upfront Thinking to Design a Better Lab Scale DoEplaced1
Presentation Given at AIChE 2009 and the Dynochem User meeting. Discussion on using mechanistic modeling to support DoE investigations and QbD initiatives for single reaction steps.
It shows the basic facts of catalyst along with its importance in industry along with its long last milestone,its characteristics & application in industry its reaction process and preparation of a solid catalyst.
Similar to Sequential Design – The Challenge Of Multiphase Systems Pd (20)
Sequential Design – The Challenge Of Multiphase Systems Pd
1. GlaxoSmithKline Jim Ward, Bob Herrmann, Teo Ching-Lay and Ann Diederich Sequential Design – the challenge of multiphase systems
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4. Conventional Modeling Approaches (2) Fractional screening and robustness are resource consuming. May have to do at a reasonable scale if equipment sensitive. Without mechanistic knowledge, number of factors is large. Route Selection Scoping Study (Scoping studies are used to narrow into the experimental region of interest) (4 Experiments) Fractional/ Screening (These designs are utilized to identify factors that affect the process) (16 Experiments) Foldover (Once the factors of interest are identified the foldover removes aliasing from the fractional design) (8 Experiments) RSM or Composite Design (utilized to determine curvature and to hone into an optimized process) Robustness Study (utilized to narrow or widen process parameters) (8 Experiments)
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6. Selected Process Isolate Hydrate via Filtration at 25 °C Agitate until Conversion Complete Charge 6 volumes Acetonitrile Heat to at least 60 C Charge Isolate Form A Anhydrate Vessel One Filter Drier Our process involves the formation of a hydrate and its subsequent desolvation to form an anhydrate (product) Greater than 20 unit operations- which factors to study?
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9. Our Approach: Dehydration Mechanism – Experimental ReactIR Filtered Saturated Solution Unstable Form charged Anhydrate Hydrate Solvate Seeded With Stable form Monitor Conversion PAT/Mechanism - ReactIR
10. Our Approach: Dehydration Mechanism – Results Theoretical Actual PAT/Mechanism - ReactIR The conversion is solvent mediated. Key factors are temperature and composition of the solvent affect solubility Hydrate Charged Concentration Time
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12. Our Approach: Desaturation Mechanism Determination Dissolution Growth Nucleation B Surface Area * Δ Cb G Δ Ca From solution to Solid A. G. Jones; Crystallization Process Systems, Pg 204 Eqs 7.36 & 7.38 simplified
13. Desaturation Mechanism - Experimental PAT / Mechanism – RC1 Monitor Thermal Conversion by RC1 Filtered Saturated Solution Unstable Form charged Unstable form charged while Seeded with Stable form Monitor Conversion Monitor Conversion
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18. Scale-Up of Selected Process DoE Robustness Kilo Pilot Plant Campaign I/II 1000x Scale Manufacturing Campaigns I/II 2000x Scale Results: Model worked well throguh kilo lab, 1000x DOE scale. Particle size changed when going to 2000x scale. Numbers acceptable, but unexplained variance
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20. New Process Design: Using solubility data to determine solvate stability regions
23. Selected Route Isolate Hydrate via Filtration at 25 °C Agitate until Conversion Complete Charge 6 volumes Acetonitrile Heat to at least 60 C Charge Isolate Form A Anhydrate Vessel One Filter Drier
24. Selected Route Isolate Hydrate via Filtration at 25 °C Agitate until Conversion Complete Charge 6 volumes Acetonitrile Heat to at least 60 C Charge Isolate Form A Anhydrate Vessel One Filter Drier
25. Selected Route Isolate Hydrate via Filtration at 25 °C Agitate until Conversion Complete Charge 6 volumes Acetonitrile Heat to at least 65 C Charge Isolate Form A Vessel One Filter Drier
26. Selected Route Isolate Hydrate via Filtration at 25 °C Agitate until Conversion Complete Charge 6 volumes Acetonitrile Heat to at least 65 C Charge Isolate Form A Vessel One Filter Drier Charge Water Charge Seeds Heat above Conversion Temp
27. Scale-up of modified process Unmodified Modified Variability Source Both variance in particle size and form issue mitigated through guided experimental design
28. Alternative Workflow Route Selection Thermodynamics (ensure the process is on stable thermodynamic footing) PAT guided mechanistic studies (kinetic model not required) Factor selection and scoping (using small scale results select factors and design space) 4 Experiments Factor investigation (DoE) 14 Experiments Robustness Study
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31. FDA Guidance A process is generally considered well understood when (1) all critical sources of variability are identified and explained; (2) variability is managed by the process; and, (3) product quality attributes can be accurately and reliably predicted over the design space established for materials used, process parameters, manufacturing, environmental, and other conditions. PAT – A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance 1 1 www.fda.gov/cder/guidance/6419fnl.pdf
32. Modeling – Statistical or Mechanistic 3 http://www.scale-up.com/usersarea/FDA/FDA_notes_28Feb08.pdf Question to the FDA “ the agency at the moment is much more tuned in to statistical models, in part due to the fact that drug product often requires statistical models in the absence of mechanistic detail” FDA Response Agreed. Statistics and DOEs should be integrated with mechanistic modeling. We do not want to see so many experiments “in the dark” as we are seeing now. Do fewer experiments. Show us that you have identified all the really critical parameters and understand the effects of all the CPPs . Notes of DynoChem presentation to FDA CDER, 28 February 2008 3
33. Mechanism – A word of caution We need a word of caution at this point. Just because the mechanism and the rate-limiting step may fit the rate data does not imply that the mechanism is correct. H. Scott Fogler Elements of Chemical Reaction Engineering, 3 RD Ed. Page 614