Tag Archives: DoE

Design of Experiments

Polymorph Form Control: Why Care About Seeding and Cooling Rates?

In Situ Monitoring of Supersaturation and Polymorphic Form of Piracetam during Batch Cooling Crystallization

Mark Barrett and others at the University College Dublin (UCD) recently published a paper Continue reading

How to Use a Crystallization Workstation to Optimize Space for Process Understanding

During crystallization development, chemists often produce crystals rapidly without time for a full Design of Experiment (DoE).  Continue reading

NESACS’s Bench to Plant Symposium

NESACS SymposiumUpon returning to the Boston area after a number of years away, I was very much looking forward to attending The Northeastern Section of the American Chemical Society (NESACS)’s Advances in Chemical Sciences “Bench to Plant” Symposium for the first time.  Held in Cambridge on October 22, about 100 scientists from the local area gathered for the one day Symposium focusing on Process R&D Chemistry, Organic Synthesis, and New Synthetic Methodology.

Some highlights of the top-notch presentations included:

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How To Optimize Peptide Synthesis

This is the second blog post in a 2 part series where I discuss the real-time monitoring of bio-based chemical synthesis. Continue reading

How To Monitor Biocatalysis in Real Time

This is the first blog post in a 2 part series in which I will discuss the real-time monitoring of bio-based chemical synthesis.

Biocatalysis continues to evolve, with the application of recombinant organisms or isolated enzymes designed to catalyze specific chemical reactions – often with highly regiospecific and stereospecific conversions. In the optimization of any chemical synthesis reaction – by traditional or biocatalyzed routes – it is not enough to simply report the yield and the enantiameric excess (ee), the kinetics of the reaction must also be considered. Understanding how the kinetics are affected by conditions such as pH and temperature allows optimization of biocatalysis through the identification of operating conditions that can ensure a maximum yield and desired ee in a timely manner. Continue reading

Quality by Design (QbD) at the BioProcess International Conference

Last week, I had the opportunity to attend the BioProcess International Conference in Providence, RI. Many of the sessions I attended highlighted the advancement of the Bio-Pharmaceutical industry in applying the principles of Quality by Design (QbD). Continue reading

How Pfizer Is Improving Process Development For Bench Scientists

Recently, Dr. Marty Guinn, Director of Chemical Development for Pharma Therapeutics at Pfizer, wrote: Continue reading

Chemical Synthesis & Optimization Supported by Design of Experiments (DoE) at Lonza Peptide


Lonza Peptide use of Design of Experiments (DoE)

Didier Monnaie of Lonza Braine presented Fast and Effective Chemical Synthesis and Optimization Supported by Design of Experiments (DoE) on May 5.  During this free online seminar, Didier Monnaie discussed how Lonza Peptide applies the Design of Experiments (DoE) concept to analyze Peptide Synthesis variables including product composition, purity, yield, and stereospecificity.

Visit the Fast and Effective Chemical Synthesis and Optimization Supported by Design of Experiments (DoE) online seminar page for more information or to view the on-demand version of this webinar.

From AAPS 2009: How To Improve Roller Compaction Processes

At the 2009 American Association of Pharmaceutical Scientists (AAPS) Annual Meeting in Los Angeles, Gerald Burke presented a case study on how Patheon Pharmaceuticals improved roller compaction processes.  Specifically, the case study focused on the influence of roller compactor settings on Critical Quality Attributes (CQAs) and the early prediction and control of granule porosity. Continue reading

Scale-up of API crystallization using Raman and FBRM Process Analytical Technology (PAT) to ensure Quality by Design (QbD)

scale-up-active-pharmaceutical-ingredients-api-american-pharmaceutical-reviewIn this recent paper published in American Pharmaceutical Review (Nov/Dec 2009) , the authors describe a comprehensive approach to QbD throughout the development and scale-up of a final crystallization step for an active pharmaceutical ingredient.

“The use of the QbD approach throughout the life-cycle of a drug product is an efficient tool for faster and more focused process development”

The paper describes the use of various tools, including:

  • Phase diagrams for a complete understanding of system thermodynamics, and determination of operating conditions to ensure production of the desired anhydrous form
  • The use of factorial design of experiments to map the operating design space, understand the effect of process variations and ensure robust operation
  • Real-time monitoring of the crystal product with FBRM (focused beam reflectance measurement) to monitor crystal nucleation and growth for optimization of seeding protocol and detection of undesirable events upon scale-up
  • In-line Raman to detect the presence of a metastable undesirable solvated form of the API, and to confirm its complete conversion to the desired stable form


http://www.americanpharmaceuticalreview.com/ViewArticle.aspx?ContentID=4504?crel=US_AC_eAdv_Blog or New Developments in Scale-Up and QbD to Ensure Control Over Product Quality, by Martin Bohlin Ph.D., Helen Jones Ph.D., & Simon Black Ph.D. Global Process R&D, AstraZeneca, American Pharmaceutical Review, Volume 12, Issue 7, November/December 2009.