Optimizing mAb Process Development for 10X Productivity

The biopharma industry is constantly evolving to meet the competitive pressures of the global market. The increasing pressure to develop therapeutics as quickly as possible, as well as a drive to decrease costs and reduce dependencies on inconsistent supply chains puts major challenges on process development (PD) departments.

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To meet the needs of today’s market, PD departments need to find ways to produce higher antibody yields and achieve greater flexibility to produce a wider variety of monoclonal antibodies (mAbs). The demand could mean large outputs of a single antibody from one batch, or many smaller batches producing different mAbs. The demands and variety required from PD today puts strain on current workflows. Overcoming such challenges require more than making multiple incremental improvements. Only a game-changing innovation will suffice. In this article, we will define such a strategy, referred to as ´Thoughtful Process Development`.

Thoughtful Process Development

Thoughtful Process Development (Thoughtful PD) starts from understanding that anything that happens in PD does not occur in a vacuum, and many different downstream groups will be affected. When developing a Thoughtful PD strategy, all the factors important for the downstream groups are considered at the very start of a project. This is essential for reducing the chance that a product gets rejected downstream--an expensive and time-consuming nightmare.

    +      There are several important factors to consider in Thoughtful PD, which are explored in greater detail in our whitepaper.

Opening a World of Possibilities

With the possibilities to reduce costs, speed up processes, and decrease risk, Thoughtful PD is well worth taking the time to think outside the box and implement. In the past, introducing a promising new technology may have seemed too risky or time-consuming to implement. Using a Thoughtful PD strategic framework minimizes those risks.

One such technology that fits well with Thoughtful PD is membrane chromatography. The technology is both easy to use at bench and pilot scale, simple to implement at a larger scale, can fit space requirements, and secures faster chromatography cycles at any scale.

    +      Learn about our Membrane Chromatography Technology: Sartobind^® Rapid A

Sartobind^® Rapid A will help your team develop a thoughtful antibody capture process for a seamless transfer forward considering procurement, MS&T, and manufacturing. The technology is both simple to evaluate at the bench, and even more simple to scale to large-scale commercial manufacturing.

    +      Download the whitepaper to learn more.

Enabling Thoughtful PD With Innovative Membrane Technology

Membrane chromatography is a useful technology for Thoughtful PD as it can easily be adapted to the needs of different downstream groups. It also overcomes many of the challenges currently associated with large-scale production using resins.

Lower Cost of Goods

It is common to purchase large quantities of materials used in resin-based chromatography in advance, requiring significant upfront capital expenditure. Not only that but a single column is packed with so much resin that it will often not be profitable after a single batch of production. Consequently, PD using resins causes a financial headache as the manufacturing plant can`t quickly amortize production costs. Membrane systems such as the Sartobind^® Rapid A require minimal upfront capital expenditure and are only used for a single batch and thus are quickly amortized.

No Cleaning Validation

As resins are used many times to make them profitable, a robust cleaning-in-place (CIP) protocol to prevent the build-up of bioburden is needed. This takes time, resources, and cost and risks damaging the resin beds. As membranes are only used for one batch and then disposed a CIP protocol is not needed. This makes both PD and manufacturing process faster and more cost-effective.

Small Storage Footprint

One problem with resin columns is that they need to be stored when not in use. As they are expensive and slow to amortize, they are often stored over a long period of time. The raw materials used to pack resin columns are also heavy and bulky. What is more, packed columns need to be stored in a cold room to reduce the risk of bioburden buildup. This all adds to the process costs. Membrane cassettes are much more compact and are fully utilized within one usage, leading to reduced costs and footprint.

Reduce PD Times With Short Cycles

One of the hallmarks of membrane chromatography is the short cycle time, which means a process can be tested and validated in PD much faster. This speed is directly translated across to tech transfer and production. Using membranes for PD means that the manufacturing group can be far more productive and produce more antibodies in less time. In addition, lifetime studies over 200 cycles take 40 hours on a membrane with a cycle time of 12 min, compared to 400 hours for resins with a cycle time of 2 hours freeing up resources and hardware. All resulting from >10X increase in indicated productivity.

The Cost of Not Using Thoughtful PD

The pressures facing PD in our industry are growing, and we need to adapt. Game-changing strategies like Thoughtful PD with membrane technologies allow you to take a holistic view of the production process and find solutions that work across different downstream groups. This approach provides you with new avenues to explore, enabling you to find new ways to meet industry demands. The risk of you not doing this is to get stuck working with heavily optimized systems trying to seek out small improvements. Doing this while the industry’s demands and pressures grow is a recipe for failure.

The simplicity, size, and cost of membranes mean that they are easy to test and validate in your current PD facility. The flexibility of membranes means that they can also benefit many downstream processes such as tech transfer and manufacture, making them the perfect way to apply Thoughtful PD.

    +      At Sartorius, we have carried out extensive benchmarking and evaluation of our Sartobind^® Rapid A, which you can read about in our latest whitepaper.