Sourcing raw materials for cell therapy manufacture – Dieter Hauwaerts, Celyad

‘Start working on raw materials early on’ – for Dieter Hauwaerts, Vice President of Operations at Celyad, the way to combat one of the biggest challenges in cell therapy manufacture is clear.

Limited availability of raw materials is a major issue for large scale manufacture of new therapies, but planning well in advance can help mitigate it: ‘In process development, take into account the quantity and quality of raw materials you will need in a clinical stage or commercial manufacturing process and build good relationships with suppliers.’

However, even with the necessary raw materials, Hauwaerts still sees issues with ‘the way we can manufacture products in a reliable and consistent way’, though he hopes that in 2017 automation will begin to negate this.

Watch the full exclusive interview with Hauwaerts – filmed at Cell Therapy Manufacturing & Gene Therapy Congress 2016 – above or here.

Continuous or intensified bioprocessing? The gold standard for improved productivity

by Nick Hutchinson

Process intensification and continuous biomanufacturing continue to attract a lot of interest within the biopharmaceutical industry as method that can increase productivity and make the most efficient use of production assets.

I interviewed Dr Gerben Zijlstra, formerly of DSM Biologics and the first named inventor on the patent for the XD® (Concentrated Fed-Batch) Technology. He now designs and implements continuous process platforms for biomanufacturers around the world for Sartorius Stedim Biotech.

What is the difference between intensified and continuous bioprocessing?

GZ: 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.

Continue reading “Continuous or intensified bioprocessing? The gold standard for improved productivity”

New analysis methods are needed for sub-visible particles in drug development

At Vironova we’re in the business of electron microscopy-based digital image analysis of sub-visible particles to provide objective and meaningful information during process development and quality control of vaccines and drug/gene delivery systems.

In current advances in drug-delivery, production of vaccines and drug formulation there are many applications for nano-sized particles such as liposomes and virus particles, and these constitute fast growing and promising technologies for new treatment development.

There are strict requirements for monitoring of processes and quality control within the pharmaceutical sector and Vironova is unrivalled in providing a comprehensive solution of analytical products and services tailored to this highly regulated environment.

Continue reading “New analysis methods are needed for sub-visible particles in drug development”

Round-up: Cell Therapy Manufacturing & Gene Therapy Digital Week

Last week we hosted the inaugural Cell Therapy Manufacturing & Gene Therapy Digital Week. An agenda of seven live webinars covered a range of the hottest topics in the industry, led by leading life science thought leaders from GSK, ISCT, Cell Medica and many more.

Every session is now available to watch on-demand at the links below. If you registered for the live event you can watch the on-demand sessions with the same login details, or if you haven’t yet registered it only takes 10 seconds.  Continue reading “Round-up: Cell Therapy Manufacturing & Gene Therapy Digital Week”

Understanding nanoparticle based processes and products

Josefina Nilsson, Head of EM services at  Vironova, is speaking on the characterization of gene therapy vectors, VLPs and whole viruses at BioProcess International Europe 2017. We asked her about nanoparticle based processes and products.

Why are modern techniques needed for a better understanding of nanoparticles in process development and production?

‘There is a need to link product understanding and process control during biopharmaceutical development. There are many parameters to track such as aggregation, changes in morphology and integrity as well as purity of particles/recombinant proteins/monoclonal antibodies. Sub-visible particle characterization is essential when comparing sample quality at different formulations or after various purification steps to achieve final product quality and stability.

We need methods that provide sufficient resolution and detailed information and that are cost-effective and adaptable to the regulatory requirements for routine drug development.

The combination of visual proof and metric values is not achievable from the currently used indirect methods like dynamic light scattering, nor is it feasible with conventional electron microscopy mainly due to the very long hours of manual work required.’

What are the challenges around regulatory expectations for nanoparticle based processes and products?

‘Methods and measurements need to be robust, reproducible, traceable and of course objective. Nanoparticles need to be visualized at high resolution to assess their purity and integrity, amongst other parameters.

The MiniTEM™ system from Vironova precisely provides the high-resolution visualization (through transmission electron microscopy) required. Automation enables accumulation of the large amount of data and analysis of the statistically relevant number of particles that are needed to produce objective measurements.

Having access to this bench-top, easy to use technology on-site and being able to routinely check samples at different phases during development omits the risk of moving too far down process design routes that will not result in desired final product quality.’

Josefina Nilsson is speaking on Day 1 of BioProcess International Europe 2017. Her talk – Characterization of Gene therapy vectors, VLPs and whole viruses from pre-formulation through process development to final manufacturing – is part of the Vaccine Manufacturing stream on 25th April in Amsterdam. To find out more and register for a pass to join 800+ bioprocessing decision makers at BPI Europe, visit the website

BPOG Five-Year Vision for Single-Use Technologies

Single-use technologies (SUT) for biomanufacturing, otherwise known as disposable technologies, have the potential to transform the industry through more cost effective solutions and solve crucial manufacturing and compliance problems. Today, suppliers have made great advances in SUT, but the vision of better, faster and lower-cost operations has not been fully realized.

Over the past two years, the BioPhorum Operations Group has been painstakingly developing best practices for SUT and work streams for extractables and leachables, user requirements and change notifications are advancing and improving the implementation of SUT. Collectively, these efforts represent thousands of man-hours and pool the knowledge and real-life experiences of many of the leading biomanufacturers embracing this technology. But much more is on the horizon.

BPOG and its member companies are developing a five-year vision for SUT, targeting a selection of SUT and auxiliary systems that are critical to ensure that SUT are a mature and established technology for biomanufacturing.

Read the full report on the American Pharmaceutical Review.

Ken Wong, Deputy Director of Process Technology at Sanofi, is presenting on this report  at BioProcess International European Summit. Join 800+ bioprocessing decision makers at the two-day event in Amsterdam on 25-26 April 2017 – find out more and register here

CDMOs & Cell Therapy Companies

A look at the evolution of regenerative medicine.

“The major gap between the cell therapy company and the CDMO is the experience in cell therapy manufacturing. The GMP environment for aseptic processing is very difficult/challenging and this is the expertise that resides with the CDMOs.”

In this interview, Ohad Karnieli, CEO of ATVIO Biotechnology and CTO/Co-Founder of Karnieli Ltd. explores the challenges that CDMOs (contract development and manufacturing organizations) need to address with Cell Therapy companies, what those challenges reveal about the evolution of the regenerative medicine industry, whether cell therapy start-ups should partner with CDMOs, and what the Israeli ecosystem means for ATVIO.

When discussing the collaborations between CDMOs and cell therapy companies, Dr. Karnieli mentions how there needs to be overlap between the different companies in order to bridge the gap and create better processes. To listen to all insights Ohad Karnieli presented us with, watch the full interview above.