Biotechnology Progress

Cover image for Vol. 30 Issue 2

Edited By: Michael M. Domach

Impact Factor: 1.853

ISI Journal Citation Reports © Ranking: 2012: 43/124 (Food Science & Technology); 94/160 (Biotechnology & Applied Microbiology)

Online ISSN: 1520-6033

Associated Title(s): AIChE Journal, Environmental Progress & Sustainable Energy, Process Safety Progress

Virtual Issue on QbD and Chemometrics

Implementation of Quality by Design (QbD) and Process Analytical Technology (PAT) for Biologicals

The concepts of Quality by Design (QbD) and Process Analytical Technology (PAT) have been gradually gaining momentum in the biotech industry since the publication of the FDA’s PAT - A Framework for Innovative Pharmaceutical Manufacturing and Quality Assurance and the ICH Q8, Q9 and Q10 guidelines. A significant effort has been made both by industry and the regulators in the last decade in partnering and solving issues that the biotech industry faces when implementing these concepts.

Despite this considerable effort, implementation of QbD and PAT in the biotech industry continues to be marred by significant challenges. While companies have started applying these concepts to a limited extent, successful approval of a QbD-PAT “application” is still awaited. The challenges seem to originate from the fact that biotech products and processes are complex. While the industry has evolved over the past decade to understand the effect of process parameters on the various product attributes, our understanding is extremely limited on the effect of the various attributes on the safety and efficacy of the product. Similarly, the effect of some of the complex raw materials that we use is also not well characterized. What everyone needs is case studies that showcase these applications and elucidate how to overcome the challenges that we face during implementation.

Biotechnology Progress has been one of the front runners with respect to publishing case studies that serve this purpose. This virtual issue highlights this fact and presents a few chosen papers that highlight the scope of the journal and the unique platform it offers. Topics that these papers address include identification of critical quality attributes (CQA), impurity characterization, high throughput process development (HTPD), process monitoring, raw material testing, computational fluid dynamics (CFD) and process modeling.

We hope that the readers enjoy this issue and feel encouraged to submit more papers that showcase implementation of QbD and PAT.

Mike Domach Anurag S. Rathore 
Editor Member, Advisory Board 
Biotechnology Progress Biotechnology Progress 

Quality attributes of recombinant therapeutic proteins: An assessment of impact on safety and efficacy as part of a quality by design development approach

Alex Eon-Duval, Hervé Broly and Ralf Gleixner

Quantitation and Characterization of Process Impurities and Extractables In Protein-Containing Solutions using Proton NMR as a General Tool

Ken Skidmore, Yung-Hsiang Kao

Chromatography process development in the QbD paradigm I. Establishing a high throughput process development (HTPD) platform as a tool for establishing “characterization space” for an ion exchange chromatography step

R. Bhambure and A. S. Rathore

Rapid quantification of protein mixture in chromatographic separation using multi-wavelength UV spectra

Mark-Henry Kamga, Hae Woo Lee, Jay Liu and Seongkyu Yoon

Strategic assay deployment as a method for countering analytical bottlenecks in high throughput process development: Case studies in ion exchange chromatography

Spyridon Konstantinidis, Eva Heldin, Sunil Chhatre, Ajoy Velayudhan and Nigel Titchener-Hooker

In situ Raman spectroscopy for simultaneous monitoring of multiple process parameters in mammalian cell culture bioreactors

Jessica Whelan, Stephen Craven and Brian Glennon

Real-time monitoring of shake flask fermentation and off gas using triple disposable noninvasive optical sensors

Xudong Ge and Govind Rao

Real-time monitoring of influenza virus production kinetics in HEK293 cell cultures

Petiot Emma, Amine Kamen

Development toward rapid and efficient screening for high performance hydrolysate lots in a recombinant monoclonal antibody manufacturing process

Ying Luo, Karisa M. Pierce

Use of computational fluid dynamics as a tool for establishing process design space for mixing in a bioreactor

A. S. Rathore, C. Sharma and A. Persad

Statistical vs. Stochastic experimental design: An experimental comparison on the example of protein refolding

Bernd Anselment, Veronika Schoemig, Christopher Kesten and Dirk Weuster-Botz