Tag Archives: Bioprocessing

Dr. Adam Elhofy – Chief Science Officer at Essential Pharmaceuticals, LLC

Adam ElhofyDr. Adam Elhofy is the Chief Science Officer at Essential Pharmaceuticals, LLC. Dr. Elhofy developed the core technology for the Ess line of products and aided in creating patents around novel uses of materials. He has over 14 years of scientific research experience in the areas of immunology, neuroscience, and oncology. He was funded by both the National Institutes of Health and the Multiple Sclerosis society as an investigator at Northwestern University Medical School.

His doctoral research won him the award of the Top 5 trainee scientists by the American Association of Immunologists. Dr. Elhofy has 14 scientific publications in peer reviewed journals. He has played a variety of roles with start-up biotech companies ranging from Principal Investigator to Director of Corporate Development.

Tell us a little about Cell-Ess and how it fills a need in the industry for bio-processing?

For Process Development Scientists and Manufacturers, Cell-Ess is a media supplement and feed that is added to CHO cell media platforms to provide an additional increase in productivity while improving protein quality.  Cell-Ess is unique in that it can be added across different clones, media schemes and cell backbones to improve titer, even in previously optimized systems.  Further, Cell-Ess increases per cell productivity, which reduces issues downstream during purification since it does not increase biomass.  Finally, Cell-Ess not only improves titer, but it also improves glycosylation, which means that one does not have to sacrifice titer for quality.

What do you hope the audience will learn from attending this webinar?

The audience will learn how lipids may be a critical and overlooked player in protein formation, production, and quality, but have been a challenge to deliver to cells due to issues with solubility and stability.  In addition, they will learn how adding in lipids via a novel delivery mechanism will aid in increasing titer.  The talk will also demonstrate how potential improvements in Golgi function increase glycan pattern consistency and higher order glycosylation.

What do you find most challenging in this industry?

We hear many different challenges when we speak with biopharmaceutical companies.  Therefore, there are several hurdles we face when collaborating with them to address their challenges.  The first is trying to understand what the objectives are of the end users.  In some cases, the stated simple objective is not really the end goal, so trying to understand the unique goals of each group has been a challenge.  Sometimes there are added hurdles for companies when they aren’t able to share their most pressing issues and needs upfront.  The second part is the much bigger challenge of crafting a method to utilize Cell-Ess within the pre-defined parameters to reach the target.  Since every biopharmaceutical company has different (sometimes proprietary) practices, we strive to ensure that our recommendations are robust enough for every scenario.

What is the most rewarding aspect of your job?

The most rewarding aspect is helping solve problems collaboratively with potential users.  There are often small windows of opportunity to work with a new and innovative product.  The window may be small due to logistical and regulatory practices already in place, so finding the best way to use the right tool at the right time is rewarding.  Of course when our solution helps a biopharmaceutical company address their current issue, it is an added bonus.

Join Dr. Elhofy and Essential Pharmaceuticals in their upcoming webinar “Mechanisms to Increase Titer While Improving Glycosylation”.  Register now!

Gerben Zijlstra – Platform Marketing Manager Continuous BioManufacturing, Sartorius-Stedim Integrated Solutions

Gerben ZijlstraDr. ir. Gerben Zijlstra received his Ph.D. from the University of Wageningen, The Netherlands.

Following his Ph.D., Gerben joined DSM Biologics in Groningen The Netherlands, where he held various positions within the process development, cGMP manufacture, and engineering departments, with a focus on introducing new (platform) processes, new process equipment into the facility and tech transfer of commercial processes to other sites.

Gerben has been involved in the process development of several commercial Bio-therapeutics, as well as platform process development (e.g. PER.C6, CHO) and technology development projects. He was part of the team responsible for the introduction of disposable stirred tank bioreactors at DSM Biologics as early as 2006. 

Gerben has worked extensively in the field of process intensification, integration and Continuous Biomanufacturing in animal cell culture. He is the first named inventor of the XD® (Concentrated Fed-Batch) technology, a highly intensified continuous cultivation mode in which cell densities of over 240 mln cells/mL and MAb titers over 27 g/L have been achieved. This technology was licensed to Amgen, amongst others, to become part of their Continuous Biomanufacturing platform toolkit.

He has furthermore contributed to the development, scale-up and tech transfer of Concentrated Fed-Batch technology to the Patheon Biologics Brisbane site for commercial scale manufacturing. This site received the 2014 ISPE facility of the year award for process innovations.

He worked as a Senior Consultant at Xendo BV in Leiden the Netherlands and was deeply involved in several Continuous BioManufacturing projects. Gerben is a regular speaker on international conferences on the topics of process intensification, process integration and continuous biomanufacturing. 

Continuous and Intensified Bioprocessing

What is the difference between intensified and continuous bioprocessing?

A fully continuous biomanufacturing process consists of interconnected continuous unit operations, without intermediate holding tanks, through which the product travels into the containers for Drug Substance in a seemingly constant flow.

Continuous unit operations represent an extremely intensified form of processing and have short downtimes relative to the amount of time they are used for production. A fully continuous biomanufacturing process might have a perfusion bioreactor coupled to a multi-column chromatography capture step, followed by flow-through virus inactivation, multi-column intermediate purification, a flow-through membrane adsorber polishing step, continuous virus filtration and a final ultrafiltration step operated in continuous mode. K.B. Konstantinov and C. Cooney have written an excellent review on this subject.

Some companies are adopting a hybrid approach to continuous biomanufacturing, such that only the upstream or part of the downstream process is operated continuously. I have seen companies operate a perfusion bioreactor in combination with a batch purification process and others that operate a fed-batch bioreactor with a continuous chromatography capture step.

The objective of process intensification, however, is to optimize the productivity of unit operations. Engineers can achieve this by using more concentrated process streams or optimizing process schedules to reduce downtime. Companies are intensifying upstream processes by increasing cell densities. They can intensify purification steps by increasing binding capacities or switching to flow-through modes that reduce processing time.

What are the relative merits of intensification versus continuous?

Both intensified and continuous bioprocessing can be used to increase productivity, reduce facility footprints and reduce costs.

Engineers may decide to intensify processes without switching to full continuous processing to retain the batch nature of a unit operation or entire process. The relatively short batch cycles allow more flexibility especially in multi-product facilities. Moreover, the batch definition is very clear and companies can keep their traditional strategies for intermediate product release. In some ways, we can consider hybrid continuous bioprocessing with concentrated fed-batch upstream processes and continuous or intensified downstream processes to be the ultimate form of process intensification that allows the retention of the batch cycle.

However, continuous upstream bioprocessing has benefits because it can result in the product spending less time in the bioreactor and near steady-state production. This can give better product quality, less variation and reduce the opportunity for product degradation. Continuous downstream is probably the most productive processing scenario. Using counter current chromatography technologies, engineers can achieve good separation of product isotypes from very similar isoforms, which may be needed during the production of biosimilars.

In your experience, which of these process scenarios is the industry adopting the most frequently?

Currently process Intensification and hybrid continuous processing are predominating. Companies are implementing process intensification strategies in state-of-the-art manufacturing platform technologies. To give some examples, some firms are using high volume and cell density seed stocks to reduce the length of the pre-culture phases prior to the inoculation of the production bioreactor. Others are using perfusion seed bioreactors to inoculate a fed-batch production bioreactor at the maximum working cell density. The use of concentrated fed-batch processing is reported increasingly.

In downstream processing, continuous capture steps are gaining momentum with the advent of new multi-column chromatography equipment suitable for commercial manufacturing. Scalable Membrane Adsorber technology is making large-scale single-use flow-through and bind-and-elute chromatography more feasible than ever.

Fully continuous processes are still mostly under development in the advanced bioprocessing centres of large pharma companies. However, we may see these in a manufacturing setting, for the production of labile products, sooner rather than later.

Which companies have experienced success with continuous or intensified bioprocessing?

Many large pharma companies, CMO’s, and several smaller biotech companies are actively working on intensified and continuous bioprocessing. Companies such as Sanofi-Genzyme, Merck, Sandoz, Bayer, Shire, Amgen, Janssen and Pfizer have all reported some form of intensified or continuous activity.

Companies with a relatively small installed asset base, but a large product pipeline, are especially interested in developing these concepts. Companies with substantial installed base are mostly interested in improving their asset utilization by applying process intensification principles.

What kind of benefits are companies seeing?

The benefits of intensification and continuous processing relate primarily to the reduced need to invest in the traditional, highly expensive production facilities especially when firms can use single-use and intensification synergistically. These approaches can also improve the quality of labile biologics and enable greater flexibility to run different molecule formats in the same facility. Finally, intensified and continuous biomanufacturing could allow more localised manufacturing strategies with companies operating many identical facilities with small-footprint across the globe.

What does the industry need in order to realise the potential of continuous or intensified bioprocessing?

Intensified and several formats of hybrid continuous bioprocessing are ready for implementation right away. Perfusion seed bioreactors and concentrated fed-batch bioreactors can be implemented today. In downstream processing multi-column capture chromatography and intensified membrane absorber chromatography are coming within reach.

Most importantly, the industry needs reliable supply partners that not only have robust high quality products and a solid supply chain, but also offer real process understanding and the engineering capabilities to translate the industries bioprocessing needs into turnkey process solutions that work.

Process development and scale-up tools, process and equipment design, automation concepts, facility layout, disposable design, are all fundamental ingredients that the supply partners should be able to offer.

How can we find out more?

If you want to know more on the status of Intensified or Continuous processing, or how to implement it, please attend the webinar I’m giving on the 24th May (2pm Berlin, 3pm London, 10am New York) by registering at http://bit.ly/2pC7LA5.

Let scientists concentrate on innovation and continuous improvement, not admin

Biopharmaceutical professionals will be familiar with the scientists’ lament about the amount of time they waste trying to track down data or, worse still, having to re-run experiments because of missing data.

The development of biological therapeutics is multifaceted by nature and increasingly requires collaboration and partnerships throughout the development value chain. Couple this with the ever-growing data volumes generated by increasingly sophisticated process equipment, and dealing with complexity becomes part of the everyday life of a biopharmaceutical professional. Such complexity frequently results in the introduction of costly errors and inefficiencies. Quality suffers, development lifecycles become longer and scientists spend an increasing amount of their time on data admin.

The cost of doing nothing

Most biopharmaceutical organizations lack a standardized, comprehensive approach to data management and quality control; with a heavy reliance on paper-based, manual processes and heterogeneous, unconnected systems. The number of participants in a typical development process is increasing, resulting in information being spread across the organization in data silos such as file stores, binders, notebooks and within people’s heads.

Studies have shown that scientists in biopharmaceutical organizations spend up to five hours per week looking for data to prepare reports. Alarmingly, often the data needed cannot be found, which can lead to experiments and even entire projects having to be re-run. This not only wastes time, but the need to purchase new reagents and materials and the increased load on expensive fixed capital assets can have a significant impact on costs.

The value of insight

By integrating data with workflows, common errors can be engineered out of processes and a ‘right first time’ approach can be realized. Bioprocessing operations can be optimized and QA overheads can be minimized. A single enterprise data management platform facilitates the flow of data across the development lifecycle and provides organizations with unparalleled insight across their products and processes.

If you’d like to hear more about how IDBS can help your scientists get back to focusing on science by optimizing your biologics development processes, then join me on October 29 for my webinar exploring this topic.

Dr Eliot Randle MBA, Head of Global Solutions Consulting, IDBS