Over the last decade, biologics, including monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), therapeutic proteins, immunotherapeutics, and therapeutic (cancer) vaccines have greatly transformed treatment of many human diseases. The pharmaceutical industry has, as a result of the therapeutic and commercial successes of  many biologics, invested heavily in these molecules. By all estimates, markets for these novel drugs is expected to increase.

However, given the competitiveness of the market of protein therapeutic, often involving multiple companies working on the development of similar therapeutics for similar targets and similar clinical indications, biopharmaceutical companies are more and more looking for innovative ways to deliver their pipeline of drug candidates, especially monoclonal antibodies and antibody-drug conjugates. Key issues in the process development of antibody manufacturing, involves maintaining desired quality attributes reduce time to market, maintain cost effectiveness, and providing manufacturing flexibility.

Photo 1.0: Lonza’s cGMP manufacturing facility in Slough, UK, located close to Heathrow Airport in London, develops therapeutic grade monoclonal antibodies and recombinant proteins. 

To meet clinical requirements and pave the way toward commercialization of antibody therapies, manufacturing capacity has, in many cases, become an issue.  Hence, to meet the strong demand, a number of pharmaceutical and biotechnology companies have built large scale manufacturing facilities containing multiple 10,000 L or larger cell culture bioreactors and supporting areas.

But, due to changing market conditions, the need for these large scale, space-consuming and hard-piped and fixed biopharmaceutical manufacturing facilities with huge stainless steel bioreactors and tanks to hold product intermediates and buffers – with their inherent inflexibility and large capital expenditures – has greatly diminished.

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While, historically, biopharmaceutical manufacturers require large scale production capacity for large volume protein therapeutics needed to meet the need of large doses over long periods, new personalized and targeted therapies require much small batch production. Furthermore, as a result, more potent protein medicines, the need for large batch production is decreasing.

Single-use Technology
With the decrease need of traditional, large-scale, facilities, novel single-use technologies have entered the market. Most of these single-use technologies are used in manufacturing processes where protein-based biologics made from mammalian cells are the target product.  In the relative short time following the introduction of single-use technologies, manufacturing has changed significantly. Given the changing demands,  as well as the increased demand for quality and improved process control, expert expect continuing change as over the next few decades. [1]

Today, only 4% of installed mammalian cell culture manufacturing capacity is based on single-use technology. Most of these single-use technologies are available for production of clinical trial materials in small volumes from 20 to 2,000 L.  However, experts believe that single-use technologies will be increasingly be used commercial manufacturing. [1]

To meet market demands, therapeutic custom manufacturing organization (CMOs), including Swiss based Lonza, a global leader in biological manufacturing, have adopted novel technologies to produce biologics. Lonza, expanded, for example, it’s mammalian production capacity at its United Kingdom facility in Slough (Thames Valley technology corridor).

As one of the world-leaders in exclusive contract manufacturing of monoclonal antibodies and recombinant proteins using mammalian cell culture, and based on the increased demand for biopharmaceutical development and clinical manufacturing services, Lonza installed two 1,000 L single-use bioreactors at the site to provide a number of quality, operational, and economic advantages. This expansion will significantly increase the existing single-use manufacturing capacity in Slough while allowing current operations to continue without interruption. The additional mammalian manufacturing capacity is now available to customers.

Compared with large scale conventional, hard-piped and fixed manufacturing systems, the availability of single-use solutions has a number of advantages. In addition to lower capital investments, shorten facility construction times a smaller footprint, increased scalability, improved mobility, higher productivity, faster turn-around – without compromising product quality – and reduced cleaning and sterilization demands and validation, some experts estimate cost savings of more than 60% compared to conventional stainless steel bioreactors.

But there is more. In addition to simplifying complex qualification and validation procedures,  the single-use bioreactors installed in Lonza’s Slough facility also reduces the risk of cross contamination and enhances biological and process safety. Furthermore, by adding reduced operating costs to the list of major benefits, it’s becomes clear why  Lonza and others contract manufacturing organizations benefit their clients by moving toward single-use technology in manufacturing.

“The ease of installation, commissioning and validation of single-use bioreactors allows us to meet the increased market demand for clinical manufacturing,” confirmed Michael Brown, Head of Operations for Clinical Development, Lonza Pharma & Biotech.

Center of Excellence
Lonza’s cGMP facility in Slough is the center of excellence for development and clinical supply. The site provides cell line construction, process development and clinical manufacturing services for mammalian-derived biotherapeutics.

Multiple scales and clinical phases
The increase in bioreactor capacity continues the implementation of single-use technologies at the Slough site and complements existing single-use equipment for both seed train systems and downstream processing, including chromatography, filtration and ultrafiltration unit operations. The new reactors are equipped with controllers that enable parallel reactor operations, expanded process capabilities with flexible operating scales and bioreactor types.

The use of these efficient, state-of-the-art, single-use technologies is expected to supports Lonza’s ability to accommodate a variety of customer projects and processes across scales and clinical phases. In turn, experts believe that it will help the company meet new technological challenges, and, more specifically, help improve and meet the need of medicine and healthcare worldwide.

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