Technical Approach

It is critical to deliver innovative and transformative technologies for achieving target product quality in the development of new, safe biotherapeutic medicines and specialty chemicals.

In the production of these products, the upstream and downstream processing is complicated, requiring many individual unit operations. Taken as a whole process, producing just a small amount of material is time-consuming and expensive, with little room for error. Many hurdles exist today that can undermine the day-to-day activities required for engineers and scientists to deliver these products efficiently.

On the pharmaceutical front, these companies must also demonstrate full knowledge of both the process and the final quality of the product to achieve successful launch and ensure patient safety.

To demonstrate this knowledge, process models, process control schemes, and proper analytics must be developed and applied from R&D to pilot to commercial scale.

However, there are challenges to doing the amount of work required to develop this knowledge in today’s environment. Reduced staff, relative to a growing pipeline, combined with the need to develop medicines faster to meet patient needs, results in an important drive to gather better data and to automate the process wherever possible.

Innovation is required, and possible, with the right attention paid to specific items, including:

  • Sample and data management, upstream and downstream.
  • Continuous manufacturing opportunities.
  • On-line measurements combined with at-line analysis (and on-line).
  • Correlation of product quality to key process variables.
  • Model-based, predictive, process control.
  • Automation of repeated analysis tasks and reporting for future reference.

To deliver data analytics solutions or new process models, for example, Alkemy Innovation works with a suite of available technologies and tools that support optimal data analytics at several levels:

  • Business Intelligence Level: “How to use business data to drive performance”
    (e.g., ERP systems like Oracle or SAP or “Manufacturing Intelligence” systems)
    1. Assessment of business needs and identification of optimal business platform.
    2. Project management for implementation of new ERP systems.

  • Engineering Intelligence Level: “How to use technical data to drive engineering decisions”
    (e.g., Seeq Data Analytics application, JMP, MVA, Process Modeling CFD software)
    1. Review of model-based, predictive, process control options.
    2. Data-driven model development and seamless integration into workflow. Including first principles-based model development and other approaches to define key trends and correlations.

  • Strategic Data Acquisition Level: “What to measure, how to measure, when to measure”
    (e.g., Process Analytical Technology assessment, Data acquisition for continuous manufacturing)
    1. Sample and data management, including data analysis, visualization, and reporting strategy development.
    2. Hardware and software technology assessment and implementation.

Partnering with Alkemy Innovation offers an effective way to achieve:

  • Increased Day-to-Day Individual & Team Productivity
  • More Timely Responses to Clients and Internal Queries
  • The elimination of Unnecessary Experimentation
  • More Insightful Q&A Leading to Smarter Conclusions Leading to Shortened Development Timelines

Example Applications:

  • Seeq Application

Seeq is a data-focused software application that enables a new way to access all important pharma process data in a single location.  This  is important for:

- Rapid investigation of process and quality data

- Reduce costs by improving operational efficiency

- Collaborate to create and share process knowledge

- Increase the value of existing data infrastructure

- Improve batch consistency and identify deviation causality

 Recent Article: BIOPHARM INTERNATIONAL NOV 2016, LEVERAGING DATA ANALYTICS INNOVATIONS TO IMPROVE PROCESS OUTCOMES—By Lisa Graham, PhD: http://www.biopharminternational.com/leveraging-data-analytics-innovations-improve-process-outcomes

 

For Example:

Seeq Data Analytics

Recent webinar:

Example technical poster presentations:

Bioprocessing Summit Poster Showing Seeq Application   BioProcess International Conference 2017

Additional Materials: 

 

  • Dielectric Spectroscopy Application

Online monitoring is essential to the development, monitoring, and control of bioprocesses. In bioreactors, one of the most important online measurements is total biomass, or viable cell volume (VCV).  

Several methods have been developed in an attempt to achieve this observability of the VCV online (e.g., oxygen-demand analysis, turbidity analysis, dielectric spectroscopy). Of these methods, dielectric spectroscopy offers numerous advantages, such as sensitivity to actual cell numbers, rapid scan rate, and capability to measure cell properties not easily accessed by other online methods.

The commercial availability of steam-sterilizable dielectric-spectroscopy probes has enabled successful adoption of this technology as a key noninvasive method to measure VCV for cell-culture processes at R&D, pilot, and commercial scale.

More information is provided here:

1) Downey, B.J., L.J. Graham, J.F. Breit, and N.K. Glutting, “A Novel Approach For Using Dielectric Spectroscopy To Predict Viable Cell Volume (VCV) in Early Process Development,”Biotechnol. Prog., doi: 10.1002/btpr.1845, published online January 11, 2014, at http://onlinelibrary.wiley.com/doi/10.1002/btpr.1845/full

2) Carvell, J., L.J. Graham, and B.J. Downey, “Insights Into Monitoring Changes in the Viable Cell Density and Cell Physiology using Scanning, Multi-Frequency Dielectric Spectroscopy, BMC Proceedings 2013, 7:S6(2013)4, available online at http://www.biomedcentral.com/1753-6561/7/S6/P4.

3) U.S. Patent, Dielectric Spectroscopy Methods and Apparatus (9568449), Issued 2/14/17.

 

Example Pharmaceutical Publications:

  • Graham, L.J., "Creating Value from Data Assets: Designing the Optimal Data Asset Management and Analytics Approach for Your Organization is Key for Improving Operations, Compliance, and Safety", Pharmaceutical Manufacturing, published September 6, 2017. Link to Article
  • Graham, L.J., "Deriving Insight at the Speed of Thought:  Advancing Medicine Production Through an Effective Data Analysis Methodology", BioProcess J, 2017; 16(1): 32–41, ISSN 1538-8766, May 8, 2017. Link to Article
  • Graham, L.J., "Leveraging Data Analytics Outcomes to Improve Process Outcomes", BioPharm International. Volume 29, Issue 11, pg 18–22, November 1, 2016. Link to Article
  • Downey, B.J., L.J. Graham, J.F. Breit, and N.K. Glutting, “A Novel Approach For Using Dielectric Spectroscopy To Predict Viable Cell Volume (VCV) in Early Process Development”, Biotechnol. Prog., doi: 10.1002/btpr.1845, published online January 11, 2014.  Link to Article

  • Challener, C.A., “Automating Online Sampling of Bioprocesses”. The Modular Automated Sampling Technology platform consists of a sterile sampling system, a sample scheduler and navigator for automated sampling and delivery of samples to analytical instruments, and a data-management system. Jul 02, 2014 Pharmaceutical Technology Volume 38, Issue 7. More at: http://www.pharmtech.com/automating-online- sampling-bioprocesses

  • Carvell, J., L.J. Graham, and B.J. Downey, “Insights Into Monitoring Changes in the Viable Cell Density and Cell Physiology using Scanning, Multi-Frequency Dielectric Spectroscopy", BMC Proceedings 2013, 7:S6(2013)4, available online at http://www.biomedcentral.com/1753-6561/7/S6/P4.

 

From Data to Direction.

Contact Info

Alkemy Innovation
alkemy@alkemyinnovation.com
541-408- 4175
Bend, OR