Tag Archives: scale-up

Early Phase Implementation of Process Analytical Technology (PAT) Tools in Chemical Development

In the pharmaceutical industry, the pressure to decrease development times for new chemical entities is common.  During the recent 17th International Process Development Conference, Terry Connelly of Pfizer discussed this particular challenge during the presentation “Examples of Early Phase Implementation of Process Analytical Technology (PAT) Tools:  Meeting Short Term Goals While Setting the Stage for Long-Term Process Understanding and Control”.
Continue reading

Importance of Mixing in Scale-up: Comparing Lab and Large Scale

Mixing Scale-up Webinar METTLER TOLEDO

Compare Lab Scale Mixing with Full Scale Process Vessel Performance

Various physical and chemical processes interact during a manufacturing or synthesis process in a stirred tank reactor, including:

  • Kinetics
  • Heat Transfer
  • Thermodynamics; Equilibrium
  • Mass transfer between phases
  • Mixing to disperse multiple phases
  • Physical property changes
  • 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

Citation:

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.

Reducing Time to Manufacturing Using Real-time In Situ FTIR Analytics as a Process Analytical Technology (PAT) Tool – On-Demand Webinar

The on-demand version of the Reducing Time to Manufacturing Using Real-time In Situ FTIR Analytics as a Process Analytical Technology (PAT) Tool webinar that I presented on January 20 is now available.

View the Reducing Time to Manufacturing On-Demand Webinar.

FTIR-Analytics-Process-Analytical-Technology-Will-Kowalchyk

During this on-demand webinar, I review case studies from the pharmaceutical industry to show how real-time mid-infrared (mid-IR) analytics provide critical information that results in shorter process development timelines, including:

  • Intermediate detection during an indazole alkylation and scale-up – Pfizer
  • Hazardous gas detection during tetrazole synthesis – Merck
  • Monitoring a Grignard reaction at the multikilogram scale – Bristol-Myers Squibb
  • Scale-up involving a sensitive enolate – Johnson and Johnson (J&J)

If you have any questions or would like to discuss this further, then please contact me.