Bio Production

Andreas Schneider, VP Life Science Alliances, Roche

1. Can you please give a brief overview of your key research interests?
Key interests are technologies that improve Life Science Research, Biological Drug Development, Biological Drug Manufacturing and patient diagnosis / biomarker
Out of that, my additional interest is the challenge of establishing information and knowledge management concepts in a global complex environment.

2. What can industry gain from this?
Safer and more efficient drugs for patients Increasing efficacy and productivity of Development and Manufacturing

3. And what work will you be presenting at the 2012 BioProduction conference?
I will present an assessment done by the global Data Management Team of ISPE PAT Community of Practice, which assessed the “readiness” of the biopharmaceutical industry to implement knowledge management in QbD environment. The team setup was a collection of big pharma companies, Academia, Suppliers and Consultants.

4. What will delegates gain by attending your presentation and session? What is the message you would like them to leave with?
Since the drug discovery, development and manufacturing process is very complex, involves a lot of unit operations and takes multiple years, people underestimate the impact of state of the art data- and information management to successfully implement Knowledge management in a QbD environment. The talk will present a concept to evaluate the own company status of readiness.

5. What is the No 1 challenge facing the bioprocessing industry at the moment?
Applying knowledge from different unit operations, because of the fast evolving environment in terms of healthcare systems, personalized medicine, regulatory bodies and analytical technology. If one would know what other people know a lot of problems would just disappear!

6. What was the last “breakthrough” technology you either bought or used?
Technology that reduced the analytical noise within the bioprocess in order to generate more useful data for our in silicon models.

7. How will the industry look in 2-3 years? What challenges will still remain/ would have been overcome?
Scientific risk based approach in QbD environment will be common standard within the large biotech company segment but small biotech and CMOs need to adopt. However, the availability of useful tools for Scientists to gain knowledge will still be a segment for significant improvement.

8. What other sessions/ talks are you interested in attending at this year’s BioProduction 2012?
I will pick individual talks from all sessions since the program is so exciting that I won’t set a general limit.

9. Are there any articles that you would recommend the audience follow that relates to your area?
The A-mAB Case Study of CMC working group (www.ispe.org) and FDA websites which discuss QbD.

10. What did you want to be when you were young?
I had no specific preference but I wanted to be in a business in which new thing can be discovered any single day. Here I am!

For more BioProduction speaker interviews click here

Interview with Mark A Kwatia, Sr. Scientist, Assay Process Design, Diagnostics Division, Abbott Laboratories

Mark A Kwatia, Sr. will be hosting on day 2 (Thursday 25 October 2012) about “Development of an orthogonal method for evaluating antibody stability and potency”

To date there is no method for determining optimal final antibody formulation and its effects on stability. This study describes the ability of new test methods to monitor stability over time. A Biacore system is used to characterise antibodies based on their potency, establishing a baseline for comparison over the course of stability testing. Accelerated stability is implemented to determine optimal antibody formulation. Antibodies prepared under multiple formulation conditions are subjected to mild heating. Samples taken periodically are tested to determine changes in purity, charge variance, and potency, thus providing optimal final formulation conditions and uncovering potential antibody stability issues.

Download an exclusive interview with Mark A Kwatia, Sr.

What are the benefits of continuous chromatography?

 

Continuous chromatography using multiple columns and a counter-current principle can improve downstream process economics in many different ways. It can increase the productivity by 10 fold; reduce the buffer demand by 50-80% and/or increase yield and purity by 50% in average. Thus, the same production output requires less installed total column volume and smaller tanks than in batch chromatography and the equipment footprint is smaller. The operational expenditures are significantly lower since less stationary phase and buffers are consumed in order to produce the same amount of material. The MIT has published together with Sandoz a study that they can save 8.5 Mio USD OPEX per year by replacing a single batch chromatography step for a single biologic by MCSGP. In addition to cost savings, continuous chromatography can also be an enabling technology in discovery, process development and manufacturing. ” By Massimo Morbidelli, ETH Zurich, Institute for Chemical and Bioengineering

Download the full article here

Dr Malkit Sami will be hosting on day 1 (Wednesday 24 October 2012) about ‘Manufacture of ImmTacs, novel therapies for cancer’ the stream will be on T cell immunity can potentially eradicate malignant cells and lead to clinical remission in a minority of cancer patients. In the majority of patients, however, there is a failure of specific immune recognition and activation mediated via the T cell receptor (TCR). Here, we describe the engineering of ImmTAC Immunemobilizing monoclonal TCRs against Cancer) suitable for use as a therapeutic agent. ImmTACs comprise of a distinct tumour-associated epitope-specific monoclonal TCR with picomolar affinity fused to a humanised anti- CD3 single-chain antibody fragment (scFv), effectively redirected T cells to kill cancer cells expressing extremely low surface epitope densities.

Download an exclusive interview with Dr Malkit here

 A Rationally Integrated Approach

Most biopharmaceutical production platforms are based on fed-batch cell culture protocols, which can support high volumetric productivity while maintaining low operational complexity (1). The industry is interested in developing or refining high-titer cell culture processes to meet increasing market demands and reduce manufacturing costs (2). Although advancements in cell engineering have enabled development of high-performing recombinant cell lines (3–6), improvements in cell culture media and process parameter settings are required to realize the maximum production potentials of those cells (7–8).

In a fed-batch process, a basal medium supports initial growth and production, and a feed medium prevents depletion of nutrients and sustains the production phase (9). Those media can contain different assortments of nutrients to accommodate the distinct metabolic requirements during different production phases. Process parameter settings — including feeding strategy and control parameters — define the chemical and physical environments suitable for cell growth and protein production. Optimization of a fed-batch process can be achieved by development efforts addressing one or more of three major elements: basal medium, feed medium, and process settings. Given the large sets of variables in these systems, establishing a cost- and time-efficient approach for process optimization is desired but challenging.” BioProcess International by Zhou Jiang, Kurt Droms, Zhaohui Geng, Susan Casnocha, Zhihua Xiao, Steve Gorfien, and Scott J. Jacobia

 
Read the full article here

Post-Conference Workshop at BioProduction

Workshop W: Implementation of QbD for Biopharmaceuticals – the Pain and the Gain
This full-day workshop concerns the theory and practice for implementation of Quality by Design (QbD) systems for biopharmaceuticals. The emphasis will be on QbD to support
drug design and manufacturing as well as biopharmaceutical comparability.

Workshop X: Comparability: Developing Strategies for Scaling Up, Tech Transfer and Other Process Changes
The objective of this workshop is to provide principles for assessing the comparability of biological products, to discuss approaches to demonstrate comparability and to review regulatory requirements. Topics to be covered include: ICH Q5E, regulatory input, demonstrating comparability at a CMC level, case studies and post marketing authorisation manufacturing process changes.

Workshop Y: Understanding Aggregation and Devising Prevention Strategies
Attend this full-day workshop to gain a critical overview of the available techniques for detection of aggregation and how these methods can be applied across bioprocessing.
Delegates will hear about strategies for combining analytical methods to ensure detection across a range of particle sizes. There will be a chance to review what is understood about the triggers of aggregation and the progress made in engineering products to reduce the risk of aggregation.

Workshop Z: Expression Systems for Antibodies and Their Fragments
This workshop offers an overview of antibody-related products and of the various expression systems available for their manufacturing focusing on the newest technologies and methods for expressing antibodies related products with improved quality and lower cost.

For more information visit the website or download the brochure.

Louisa Maitland
Bioproduction Researcher Manager
Informa Life sciences

Pre-Conference Workshops at BioProduction

Site Visit R: TU Berlin and Medical Biotechnology
The Bioprocess Engineering department, devotes its research activities to the area of biocatalysis, specifically to the design of new engineered biocatalysts and to the methods of their development. Aside from molecular biology laboratories the visitors will see the bioprocess pilot plant, the high throughput laboratory together with a short presentation of the key projects of the chair and the Institute of Biotechnology. Please join us in the afternoon following the workshops to visit these interesting laboratories.

Workshop S: Practical Technology Transfer for Biopharmaceuticals
Technology Transfer can easily make the difference between a successful or failed project and it is therefore essential in getting it right the first time.  In this workshop we will look at how to derive, implement and manage a successful technology transfer project; lifting technology transfer off the page and putting it into practical context that can be readily applied in the field.  The One day interactive workshop will look at the principles and practices of technology transfer, how to assemble the nuts and bolts, case study scenarios and problem based team challenges.

Workshop T: Analytical Tools Helping to Develop and Solve Issues with Formulation
One of the troubling and challenging tasks in the development of protein pharmaceuticals is to deal with their physical and chemical instabilities. Materials in contact by our protein pharmaceuticals during a manufacturing process are numerous. The phenomena of adsorption of our drug substance on the surface of  container are more and more suspected. They can have a huge impact on either the accuracy of the dose of protein administered or the structure of the protein (for example the most common physical instability is aggregation and apparition of particles).  Proper and adequate analytical methods have to be used to ensure successful development of quality protein products.

Workshop U: Biopharmaceutical Fundamentals
This workshop introduces the audience into the world of biopharmaceutical, the practical outcome of the 30+ year biotechnology revolution, by describing the critical scientific, safety, efficacy, manufacturing, clinical, regulatory, marketing and legal issues influencing the discovery, development, and commercialisation of these products.

Workshop V: Mixed Mode Chromatography Strategies for Biomolecule Production
A majority of monoclonal antibodies are purified using affinity or protein A. For each non-antibody therapeutic in today’s pipeline the lack of an affinity capture increases the burden on every step of the downstream process to achieve final product purity. Mixed mode media have a significant role in polishing for monoclonal applications, and are now being leveraged into capture, intermediate and polishing steps for new protein therapeutics.

For more information visit the website or download the brochure.

Louisa Maitland
Bioproduction Researcher Manager
Informa Life sciences

Immunogenicity Concerns and Extensions to other classes of Drugs

 ”Small-molecule treatments are invaluable in providing symptomatic benefits for an array of illnesses. However, many serious conditions — ranging from cancer to autoimmune disorders — respond better to more sophisticated complex drugs such as therapeutic biologics and nonbiologic complex drugs (NBCDs). The latter are medicinal, nonbiological products in which the active substance is not a homomolecular structure, but rather consists of a number of different (closely related) structures that cannot be fully characterized. The US Food and Drug Administration (FDA) defines a therapeutic biologic as “a protein derived from living material (such as cells or tissues) used to treat or cure disease” (1).
 Until recently, pharmaceutical companies in the United States had no procedure to follow when submitting applications for “generic” or follow-on versions of biologic drugs (now called biosimilars). And still, no clear guidelines are available for NBCDs. Despite expiring patents on biologics, this was a complicated issue because even slight changes in protein structure (such as small differences in amino-acid sequence) could cause serious side effects (e.g., immunogenic reactions) in patients.” BioProcess International by Vera Weinstein

Read the full article here

“It is estimated that hundreds of new recombinant proteins and monoclonal antibodies (MAbs) enter preclinical and clinical development each year (1, 2). Concomitant global competition in biologics manufacturing has put immense pressure to shorten the time to market. Over the years, cells from various origins have been used for therapeutic protein production (2, 3–5). One of the most economical choices is Escherichia coli, used to make proteins such as human insulin and growth hormone. But the bacteria have some serious shortcomings, such as an inability to perform posttranslational protein modifications (6). Mammalian cell lines such as Chinese hamster ovary (CHO) cells, baby hamster kidney (BHK) cells, or human fibrosarcoma cells have addressed necessary glycosylation in production of certain therapeutic proteins (6). For MAbs, CHO and NS0 cell lines are the most commonly used expression hosts (2, 4).” By BioProcess International

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By Vishal Agrawal, PhD, scientist,  bioproduction group,  Aragen Bioscience
Manjot Bal, PhD, scientist,  University of Texas Southwestern Medical Center’s department of neuroscience in Dallas

 If so Bioproduction Conference and Exhibition 2012 is your must attend event for 2012!

This year we are launching 4 new tailored conference tracks, so all your manufacturing solutions will be answered under one roof. We have a dedicaded stream on Upstream and Analytical Support for Antibodies and Non Antibodies which will concentrating on:

• Latest advances in cell line development – Find out the latest processes on microbial cell line systems for antibodies and non-antibodies, as well as the latest updates on metabolomics and how this information is being used in practice. You will also hear Industry case studies on upstream manufacturability to help streamline and speed up your cell line development process for both antibodies and novel therapeutics
• Streamlining and optimising upstream processing - learn how to overcome the bioprocessing challenges of using non-antibodies
• Key analytical and formulation barriers facing the developments of biosimilars – Understand the manufacturing challenges faced with biosimilars and how they have been overcome to ensure regulatory approval and hear the latest analytical work  carried out
• Advances in high-throughput analytics -  Hear the latest on high-throughput analytical methods for improving bioprocessing and the advantages this will have on your manufacturing process
• Glycosylation – Review  the lastest developments with glycosylation and other post-translational modifications and understand the mechanism of action within this process.
• The role of analytics to optimise upstream development – Catch the latest, cutting-edge analytical methods being used to characterise biologics and optimise upstream and downstream processing. You will also gain an insight into the latest advances with novel analytical technology that is available
• Exclusive workshop focussing on Upstream and Analytical Support for Antibodies and Non Antibodies : Workshop Z- Expression systems for antibodies and their fragments focussing on the newest technologies and methods for expressing antibody related products whilst improving  quality and lowering cost

Louisa Maitland
Bioproduction Researcher Manager
Informa Life sciences