Efficient Integration of Single-Use Equipment During Capacity Expansion Projects

By Nick Hutchinson

More than ever before, biopharmaceutical companies are able to establish their own in-house biomanufacturing capabilities. The adoption of single-use technology has reduced the need for expensive utilities systems and large manufacturing footprints. The inherent flexibility of this technology is allowing firms to connect steps in the production process with relative ease and without the need for fixed stainless steel pipework. Upfront capital costs have diminished and although operating costs remain, they are incurred only when the success of a drug candidate or licensed product warrants further production. Thus, single-use technologies provide a means to mitigate the risk of wasting large capital expenditures in the event a molecule is unsuccessful in the clinic or on the market.

Good engineering practices are key

Single-use technology is available for nearly every step in a biopharmaceutical manufacturing process below a certain scale of production. Biologics such as monoclonal antibodies and viral vaccines can be produced using processes in which the entire product, media and buffer flow-paths are disposable. However, companies attempting to install or expand new biomanufacturing capacity should be mindful that they should follow good engineering practices to maximize the probability of success. Despite the ease with which firms can install single-use capacity, relative to traditional stainless steel projects, this can nevertheless lead to an insufficient consideration of how firms should integrate single-use equipment with other steps in the process chain. The overlooking of proper integration can lead to incorrect equipment sizing, poor equipment design or an incomplete solution being developed. This can result in process failures, delays and the need to perform costly engineering rework.

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Affordable Biologic Downstream Purification with Single-Use Protein A Membrane

This article was originally published on www.DownstreamColumn.com by Brandy Sargent, Editor in Chief

At this year’s Biotech Week Boston there were many exciting talks on downstream purification and associated new technologies. In particular, there were several talks about optimizing the downstream purification process. One very interesting talk, given by Renaud Jacquemart, PhD Principal Scientist, Director Vaccines Process Sciences, was titled “Enabling Manufacturing Of Affordable Biologics Through The Use Of A Protein A Membrane
 In A Single-Use Purification Strategy ” and focused on the application of a fully single-use chromatography purification process in place of resins. This strategy envisions the use of a unique Protein A membrane for which Natrix recently signed collaboration agreements with Merck & Co. and Sanofi.

Creating a more affordable purification strategy

In his talk, Dr. Jacquemart begins by talking about the goal of creating a more affordable purification strategy and how the Natrix approach incorporates a holistic vision of the entire manufacturing process. To meaningfully decrease total cost and create the most efficient process, companies must significantly reduce the physical scale of manufacturing facilities and enable greater flexibility. This permits faster turnaround and accommodates a wider range of scales and products for any given time period. Achieving these goals requires a large increase in productivity and much-simplified single-use architecture for purification.

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Supplier Capabilities Underscore Their Value Creation Potential

By Dr. Nick Hutchinson

The introduction of single-use technologies into biomanufacturing process increasingly requires the industry to operate as a cohesive network of organizations that function across all levels of the supply chain to ensure the safe and efficient production of biopharmaceuticals.

Biomanufacturers engage in a variety of activities that require them to work with suppliers ranging from the replacement of existing production equipment in established processes through to the development, manufacture and introduction of innovative, new-to-world biologics products. The nature of these projects influences the type of relationship that biomanufacturers will seek from their suppliers

KE Kristian Möller and Pekka Törrönen, working at the Helsinki School of Economic and Business Administration, published an article describing a spectrum on which a business’ projects may sit (Möller & Pekka, 2003). At one end of the spectrum lie projects in which firms are attempting to gain maximum efficiency from existing resources and technology and require a low level of relational complexity with their suppliers. At the opposite end of the spectrum are those future-orientated partnerships in which actors in the network co-create value and can lead to radical innovations that open up new business opportunities.

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Single-Use Technology and Modular Construction

Innovative strategies for creating flexibility in new and legacy biomanufacturing facilities

Transitioning away from stainless steel to disposables has been an important industry trend. According to a 2015 report by BioPlan Associates, 90% of biomanufacturing facilities are using single use/ disposable technologies to some degree and 69% of manufacturers and suppliers report performance improvements over the previous 12 month period due to the use of disposables. Disposable systems come pre-sterilized, which provides the benefit of a significant reduction in switchover and setup times with the elimination of cleaning and sterilization steps. This results in flexibility for manufacturers to quickly change their product lines to adapt to market needs. Leading pharmaceutical manufacturers are considering the business case for the variety of options that are now available at almost every step of the production process. Single-use technologies help to reduce both fixed and consumable capital expenditures and increase operational efficiencies.  The reduction in overall operating costs stems from reduced maintenance, sterilization, clean steam, chemicals, and energy demand. Smaller runs are particularly amenable to single-use technology, as most disposable systems can produce 2,000 liters at maximum production, considerably less than the 10,000-25,000 liter production scale of many pharmaceuticals.

Another critical aspect important in newly designed or re-designed facilities is that disposable products are inherently more modular and flexible. This provides cost-savings options for manufacturing many different products in small volume using the same floor space that would have been used for a single product in a traditional model. There is also enhanced protection against cross-contamination, making it more rapid and efficient to switch between multiple products.

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BioPhorum Operations Group’s (BPOG) Best Practices Guideline for Mitigating Risk from Leachables

The BioPhorum Operations Group’s (BPOG) Best Practices Guideline for Mitigating Risk from Leachables in Polymeric Single-Use Components Used in Biomanufacturing will be presented at BioProduction, Dublin in October 2016.  This leachables guidance builds upon the success of the BPOG Extractables Protocol to form a completed picture of the impact of using Single Use Systems (SUSs) for the biopharmaceutical industry.

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Leachables Testing Methods & Best Practices

Author: Nick Hutchinson

BPOG’s Best Practice Guide

The biopharmaceutical industry is increasingly using Single-use systems (SUS) for the manufacturing of medicines. Furthermore, companies are applying the technology in applications that are more critical to patient safety. Methods for assessing risks associated with using SUS in bioprocessing need to be developed.

Miriam Monge, Marketing Director for Integrated Solutions at Sartorius Stedim Biotech moderated a session at the BioProcess International Conference & Exhibition, 2016 in which representatives from the BioPhorum Operations Group (BPOG) discussed best practices for leachables testing when implementing SUS. During her introduction, Monge highlighted the need for the various stakeholder in the industry to work together to find consensus on testing methods.

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Applications of Single-Use/Disposable Technology in Fill/Finish [Whitepaper]

Whitepaper Overview:

A range of factors are currently conspiring to push the field of pharmaceutical manufacturing toward wider use of SUSs. While factors specific to the fill/finish stage have meant that it has taken the longest to be affected by such changes, recent developments in the associated materials, technology and regulatory landscape are making possible rapid development on this front. Disposables have the potential to render substantial benefits in respect of savings of time and expense, and enhancements to safety and clinical rigor. All this makes it almost certain that they will see continued growth in the immediate future, and anyone with a stake in the industry would do well to keep a finger on the pulse of this transformation.

The CMO Patheon has installed an entirely disposable fill/finish system that is fully validated, scalable from 2 liters to 200 liters, and meets all requirements in respect of E&Ls.[1] Fill sets of three different sizes were manufactured in collaboration with suppliers. An initial saving of 10% on capital investment was achieved through the implementation of a single-use system, and subsequent continuing benefits include a reduction in personnel hours required for changeover from 19 hours to 1.5. Further, the flexibility offered by SUSs in terms of size means that excess or wasted capacity is greatly reduced, and Tony Pidgeon, senior manager of global science and technology at Patheon, claims, “At this point, whenever we can, we will opt for single-use systems, and single-use technology has become the preferred approach for new facilities.”[1]

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