The future of biomanufacturing with Christian Eckermann, Boehringer Ingelheim

At BioProcess International European Summit, we sat down with Christian Eckermann, Head of Biopharma Austria and Member of the Biopharma Executive Committee at Boehringer Ingelheim, for an exclusive interview. We discussed next generation bioprocessing and facility implementation and the challenges that still need to be overcome to achieve it.

Watch the full interview above or here.

What are the biggest challenges that need to be overcome in bioprocessing?

CE: ‘One of the biggest challenges is…to be more effective in operation, but also in development; to have more effective high performance processes. Especially with the higher titres there will be a major press on downstream processing and there’s some innovation needed to improve the downstream part of it.

There are also some challenges with the new opportunities having new molecules, more designer molecules, moving away from the typical antibodies to biospecifics and other design formats. There is the development part to get to the market quickly, and the operations part with all the data there is a big opportunity and also a challenge to fully leverage that opportunity.’

Where do you see bioprocessing and facilities in 5 years? What are the biggest changes you expect to see?

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16 Million People (and counting) Saved From Paralysis

Poliovirus and one of the Science Heroes that made this Headline Possible: Eckard Wimmer, Ph.D.

Polio has been around for centuries – but it’s almost gone – thanks to the efforts of many scientists, such as Drs. Jonas Salk and Albert Sabin, as well as Eckard Wimmer, Ph.D., a National Academy of Sciences Scholar. Polio was first described clinically back in 1789 but it wasn’t until nearly a century later in 1894 that the first polio epidemic occurred. Polio peaked in 1952 when 3,145 people died and thousands more were paralyzed[1]. Around this time, the first vaccines were introduced which had a profound impact reducing the incidence of this disease and inspired one scientist in particular who went on to achieve breakthroughs in poliovirus after fleeing Berlin at the height of WWII, then later fleeing East Germany to continue his studies.

Dr. Wimmer, then a chemist, became fascinated by poliovirus as the first example of a self-replicating chemical and pathogenic entity, “a chemical with a life cycle”, and dug in to research its biology[2][3]. He and his lab were the first to sequence a eukaryotic RNA virus. They also elucidated its unique structure[4] (the first RNA virus to be linked to a protein later discovered to be involved in RNA replication) as well as to decipher the genetic organization of the poliovirus genome. These groundbreaking efforts enabled Dr. Wimmer to chemically synthesize the poliovirus genome – essentially becoming the first to successfully synthesize a living organism outside a cell[5]. In short, the world’s first test-tube virus was “born”, and, along with it, the dawning of the age of synthetic biology.

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Who are the competent biomanufacturers?

by Nick Hutchinson

Once upon a time, this seemed like a very easy question to answer. Engineering companies designed facilities with stainless steel equipment to the user requirement specifications of their biomanufacturing customers. These biotech companies then operated the facilities, producing quantities of product to supply the market. They understood these products, having developed them in-house, and had designed, characterized and scaled-up the required bioprocess. They put in place the quality systems necessary to ensure the safety of their patients. In short, these biopharma companies were vertically integrated with competencies in developing, producing and marketing their products in a tightly regulated market. To better serve their customers they invested in manufacturing sciences leading to process innovations that lowered costs, increased throughput and improved product quality.

Leading biopharmaceutical firms still see biomanufacturing as a core competence. Amgen, to give one example, proudly states in its 2016 Annual Report that the company’s “long record of delivering reliable supplies of high-quality medicines with improving efficiency is a source of differentiated competitive advantage”.

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The importance of creative solutions in cell therapies

Pim Hermans, Director of Ligand Discovery at Thermo Fisher Scientifics, emphasises the importance of the symbiotic relationship Thermo Fisher has with their customers. For Hermans, this was key for their breakthrough product – ‘affinity products…for purification of biotherapeutics’ – which has been ‘really adopted by the industry’. It is widely used in the manufacturing of medicines, ‘especially in the gene and cell therapy field’. His example is the current use of AAV, which is now being used in ‘manufacturing at a large scale’.

By seeing customers as partners, Hermans’ philosophy is that ‘together we can make our products to suit the needs of their molecules’. He is confident in their ability to produce intuitive products and ‘do the best we can to provide the solutions’. He acknowledges ‘it can be challenging, but we are there to face those challenges together to try to solve problems to make good products’. This has been paramount to the evolution of cell and gene therapies.

Speaking of the new projects Thermo Fisher are currently working on, Hermans talks of the ‘next stage’ that will result from gene therapy evolution. He highlights the lentivirus as a new challenge, due to its nature as a more demanding viral vector, but a challenge he is eager to embrace.

Watch the full interview, filmed at Cell Therapy Manufacturing & Gene Therapy Congress, with Pim Hermans above or here.

Developing automated cell processing strategies with Olivier Waridel, GE

As previously the CEO of medical device company Biosafe and now GM of Cell Banking & Point of Care at GE Healthcare, Olivier Waridel understandably feels positive about the recent partnership between the two companies. For him, the collaboration broadens the possibilities for both companies, ultimately working towards a ‘full solution for players in the CAR-T and immunotherapy space’.

‘Automatising’ cell processing is one of the developments Waridel has worked on and is most proud of. Using the example of cord blood banking Waridel outlines the process development ‘all the way from a sample in a bag to the cyro-preservation tank…[we] developed the tools for the whole processing of that in the laboratory’.

Cord blood banking is just one such example, and Waridel goes on to explain his work in ‘the clinical trials going on in the regenerative medicine space where it is required to have a closed system and automation for orthopaedic, cardiovascular and other trials that are going on. Our instruments can automate the process in the operating room; getting the cells ready for the re-infusion into the patient.’

The cell therapy space is a natural progression for Biosafe, allowing them to build on their previous experience of automating the cell processing line. Waridel explains how they use the same technology they already employ, but are also introducing a new instrument, Sefia, which has been specifically developed for the cell therapy space. Sefia will assist them with ‘running through the different cell manipulations and will help with the delivery to the end patient’.

In terms of differentiating their product from similar instruments on the market, Waridel highlights that Biosafe’s is centrifugation based:

‘The beauty is the technology in itself, so it allows us to process volumes and the way the cells are centrifuged allows us to go into detail into which lap of cells we are collecting and offers a lot of flexibility.’

The technology also allows them to include customers within the process development, building increasingly fluid relationships. Waridel aims to increase ‘reliability and stability’, and therefore increase the number of patients they can treat.

Watch the full interview, filmed at Cell Therapy Manufacturing & Gene Therapy Congress, with Olivier Waridel above, or here.

‘The emerging technology revolution that is our cell and gene therapy space’

The gene editing tools and strategies for successfully taking a gene therapy to market.

Michael Mendicino, Owner, Chief Consultant & Advisor at Hybrid Concepts International, is excited to ‘be part of the emerging technology revolution that is our cell and gene therapy space’. We caught up with him at Cell Therapy Manufacturing & Gene Therapy Congress to discuss the current trends in gene therapies.

For Mendicino, the improvement in gene editing technologies is one of the most important recent developments in the industry. Although not necessarily a new or unfamiliar concept, he emphasises that the new technologies that are continuously emerging, such as Zinc Finger, TALENs and CRISPR, are vital to the future of gene therapies.

Mendicino sees a number of potential breakthroughs that are currently in the process of development that will allow for these new technologies to become viable treatment options:

‘For 2017 everyone is looking to see a licenser for marketing authorisation for the CAR-T product either coming from Novartis or from Kite Pharma. I think that will be tremendous for the field and will legitimise the field, not only for the companies that apply for the BLA (Biologics License Application) and get approval , but also for other companies that are not that far behind them, specifically in the CAR-T space, but also in cell and gene related product spaces.’

When building a BLA strategy that meets all the requirements, Mendicino breaks it down into three disciplines that need to be considered separately, as well as in conjunction with each other. Firstly, there is the ‘chemistry, manufacturing or controls’, or the ‘quality’ of the product. The second is ‘pharmacology and toxicology’, also known as the ‘pre-clinical or the non-clinical’, and the third is the clinical. Often these three considerations are handled in parallel, but this may need revising throughout the process. This is due to factors such as the product itself, as well as ‘the clinical indications sought, the patient population, the recruitment rates and whether or not the company has gone through some major CMC change that required scale up for commercial inventory.’

Watch the full interview as Michael Mendicino explores the methods of helping gene therapies progress to market above or here.

Comparability for advanced therapy medicinal products with Christopher Bravery

For a recent KNect365 webinar, Christopher Bravery from Advanced Biologicals discussed the challenges of comparability for the ‘more complex’ biological molecules. He went into a detailed examination of purification, characterisation and activation, and their position within the space of biological comparability. Here we summarise the in-depth discussion that offers guidance and advice for those looking to meet the requirements of comparability for their molecules. 

LISTEN TO THE WEBINAR HERE

First, Bravery outlines the differences between small molecules and biologicals which makes the characterisation of them a greater challenge for pharmaceutical companies. For small molecules, it is possible to know the exact molecular structure. When a cell substrate is introduced, the ‘manufacturing process is less clear’ as the ‘windows of characterisation are fogged with variability.’ This makes comparability much more challenging for cell based products as you are unable to define the molecular structure as easily. The proteins and the cell itself all vary in their phenotype, and are often more heterogenous, which adds to the uncertainty in the measurements taken.

Bravery defines comparability for biologics as the ‘need for a change in the process’ when the development is incomplete, either at post-approval or late stage. At this point, you should have characterised the raw materials to ‘understand critical quality attributes to establish process parameters’. He uses a hypothetical case study for a CAR-T product to demonstrate where comparability can need to be used within a development system, highlighting the area of ‘activation.’ (see diagram top)

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