This year was the first year that the BioProcess International Conference (BPI East) became Boston Biotech Week and incorporated a Cell Therapy track. I was excited to attend and to see what the format for the new conference was going to be. I felt that the content was very relevant and covered a wide breadth of topics, from cell culture to commercial manufacturing and I was particularly interested to see how this translated to cell therapy. Overall Boston Biotech Week delivered talks focused on improving the manufacturing process for biopharmaceuticals and cell therapies, enabled industry networking opportunities, and provided the chance to see the latest products and technologies.

One area that I focused on was downstream manufacturing including recovery and purification, and drug product manufacturing including fill/finish.

Recovery and Purification

One of the most discussed topics of Boston Biotech week was Continuous Processing and this included Continuous Processing in Downstream. Another hot topic was getting the most out of your purification investment including improved utilization, single-use opportunities and optimization strategies.

Other topics discussed included:

• Navigating the junction of upstream and downstream to make it more efficient
• Incorporating high throughput and process modeling to improve both legacy and new processes
• Purification of microbial systems
• Virus purification

Selection of talks and announcements:

End-to-End Integrated Continuous BioProcessing Platform for Biologics Manufacturing

Engin Ayturk, Ph.D., R&D Manager, BioPharm Applications at Pall, gave a talk titled, “End-to-End Integrated Continuous BioProcessing Platform for Biologics Manufacturing,” updating the status of their continuous process portfolio. In the talk Dr. Ayturk, highlighted the company’s capabilities with respect to a fully continuous process. In downstream, they have introduced their new Cadence line, which includes the Cadence Acoustic Separator, the Cadence Inline Concentrator, the Cadence BIOSMB PD System for continuous chromatography, and the Cadence Inline Diafiltration.

Unlocking Downstream Efficiency

Günter Jagschies, Ph.D., Senior Director, Strategic Customer Relations, GE Healthcare BioProcess Division, gave a talk titled “Unlocking Downstream Efficiency.” In the talk he highlighted several trends being seen in downstream processing, including:

• Continuous manufacturing: Improved productivity, improved resin utilization, lower COGS
• Connected Processing: Combining unit operations, reduce cycle time.
• Higher demands on facility utilization: Smaller, more flexible unit operations

As a result, there is demand for downstream process solutions to keep up with new trends and applications.

Dr. Jagschies went on to highlight improvements that have been made in downstream technologies, for example in the 1990’s mAb production costs were $500-$1,000 per gram, today production costs are down to $50-100 per gram. In addition downstream efficiency has been improved to keep up with upstream improvements including higher titers. Protein A binding capacity has increased from 15g/L to up to 60g/L. There has also been the introduction of single use technologies and the scale down of larger facilities.

Other improvements in Protein A include:

• Modern column packing system (packing methods are integrated into automated operations), resulting in reproducible, consistent, packing.
• Leveraging functionally closed systems and automating as much as possible. Automated column packing saves costs due to error and loss.
• Prepacked columns may make sense to some users depending on scale of manufacturing.   Prepacked Protein A is limited to larger scale as only 60 cm columns are available.

Either automated self-packing or pre-packed columns may prove favorable depending on your operation scale and experience.

There have also been efficiency improvements in chromatography systems. For example, GE’s ÄKTA pcc (periodic counter-current) 75 chromatography system has 3 or 4 column models.   Three or four columns are sufficient to cover large scale manufacturing due to newer higher capacity resins.  This system is highly automated with dynamic control.  The system manages many functions including the amount of load.  Load is calculated from sensors and the system provides the amount needed without human intervention.  This increase in automation provides more consistent operations and a reduction in operator time.

Areas for improvement as identified by Dr. Jagschies include, a gap in continuous processing in the area of viral clearance. Virus clearance is not very amenable to continuous process and needs further development to achieve true continuous flow processing.

In addition, buffer preparation and medium preparation is an area to investigate for cost reduction. Currently, buffer and medium preparations are about 25% of total cost.

• Mixing inline can reduce storage volumes 10X and result in a 35% reduction in footprint.
• Connected processing increases efficiency by reducing hold times and storage.

Single-Use Primary Capture Technology with the Promise to Deliver New Standards for the Economics, Convenience and Reliability of mAb Bioprocessing

Another interesting talk titled, “Single-Use Primary Capture Technology with the Promise to Deliver New Standards for the Economics, Convenience and Reliability of mAb Bioprocessing,” was given on by Oliver Hardick, Ph.D., CEO, Puridify. In the talk, Dr. Hardick described their single use Protein A product, which was a finalist for the BPI Award for best technology – Downstream and won for best collaboration with GSK. At Puridify they have developed a single-use Protein A column that is efficient and cost effective. Through collaboration with GSK, they were able to confirm commercial relevance and GSK reported a 6% savings on cost of goods, plus additional savings on CIP and validation in a case study. When modeled through Biopharm Services, they found a 24% estimated savings on cost of goods in multiproduct facilities. The product is not commercially available yet.

Purolite Life Sciences’ state of the art new agarose manufacturing facility set for completion in 2017

Purolite Life Sciences has announced that their new manufacturing facility is scheduled for completion in 2017 in South Wales. This facility will increase Purolite’s annual production capacity to provide 30% of the world’s agarose demand. It will be capable of producing 100,000L of high flow agarose resin for their Praesto® range of ion-exchange and Protein A affinity resins, designed for the purification of monoclonal antibodies. This facility ensures security of supply and dual sourcing. It realizes one of Purolite Life Sciences’ missions, which is enabling secure dual-sourcing of high-performance agarose resins, thereby minimizing supply chain risks for drug manufacturers without compromising resin performance.

Duncan Sinclair, Plant Manager for Purolite Life Sciences Agarose said, “Security of supply is a key requirement within our industry and this investment confirms Purolite’s commitment to the long term supply of our high flow agarose range of Praesto products. Purolite has been based in Wales since 1982 and the location is in an extremely stable political, geological and meteorological environment.”

Chris Major, Sales Director for Purolite Life Sciences Agarose also adds, “Purolite’s 35 years of heritage and expertise in developing large-scale manufacturing facilities globally, as well as our established global distribution network, ensures that we can reduce lead times to deliver the highest-quality agarose resins as efficiently as possible.”

You can “fly through” the new facility by watching the video below:

https://youtu.be/C2Q8nv8TxDQ

Drug Product Manufacturing and Fill-Finish Processing

This is by no means an exhaustive list, but some highlights of the talks I attended include:

• Stability and solubility issues with challenging proteins and ADCs
• Unique challenges of finish/fill for non-standard or emerging modalities
• New fill/finish technologies
• Strategies for integrating drug and device development with patient experiences to provide best care
• Technology Transfer to CMOs best practices
• Liquid shipping of drug product in single-use bags
• Process characterization of filling operations to ensure quality attributes

I will cover several of these areas in more detail in the coming weeks – stay tuned.

Don’t miss BioProcess International West – BPI West in San Francisco February 27- March 2, 2017