Initially discussing the latest trends in the biopharma industry, Adam notes that process analytical technology (PAT) has seen significant evolution in recent years and become an important component in terms of accelerating development timelines. PAT solutions enable the simple scaling of manufacturing processes to facilitate the production of biologics and cell and gene therapies (CGTs).
AG: Recently, the incorporation of PAT probes into single-use bioreactors (SUB) to track cell growth, metabolite by-products and automated SUB feeding strategies has been trending as it allows biopharma companies to optimise both development and production runs. PAT is also being included in downstream processing protocols, which provides access to real-time measurements and feedback — while also
automating the control of downstream systems (chromatography and formulation skids) to allow for faster and more accurate throughput. These PAT technologies are being developed with novel artificial intelligence (AI) and machine learning technologies.
Another trend we’ve been seeing recently is the integration of AI with multi-omics data. Genomics, proteomics and metabolomics are all helping to accelerate research and enhance early intensified process development. Large data sets are created from the development and integration of PAT; these can then be assessed to guide how companies create downstream processing protocols, allowing efforts to be better planned and more successful.
AKA: How can single-use bioprocessing materials benefit the biopharmaceutical industry?
AG: Single-use technologies (SUTs) for bioprocessing offer significant advantages compared with traditional stainless steel systems, which make them an increasingly popular choice for biopharmaceutical manufacturers. SUTs can boost the sustainability, flexibility and scalability of the CGT manufacturing process while also contributing to systemic cost reductions and lowering its environmental impact.
Stainless steel technologies require strict sterilisation and cleaning protocols, which can increase water consumption and overall energy use within facilities. By contrast, SUTs eliminate the need for these processes, helping manufacturers to achieve their sustainability goals by reducing water, chemical and energy usage. On top of that, newer, higher-performing SUBs have been shown to lower consumable costs
by as much as 37% compared with stainless steel alternatives.
SUTs also enable shorter setup times and allow for easy reactor size customisation and configuration, which can lead to more accurate volume projections. With the ability to be easily multiplexed, SUTs support large batch production without the need for dedicated infrastructure.
AKA: What are the benefits of using biobased films in the biologics manufacturing process?
AG: Biopharmaceutical manufacturers face several challenges in their day-to-day operations, including keeping up with demand, reducing their environmental impact and complying with new regulations. It’s critical for commercial manufacturers to choose solutions that not only enhance efficiency, reduce costs and boost yield, but also help them to achieve their sustainability goals and commitments.
As an increasing number of companies begin to replace their steel systems with single-use, biobased films, the need for a more sustainable SUT becomes more important. Biobased films can offer biopharma companies the opportunity to improve their sustainability credentials while enhancing their safety and cost efficiency; this makes them an attractive option for manufacturers that are seeking to reduce their
environmental impact while still maintaining high quality standards. Biobased films tend to perform in the same way as plastic polymer-based versions, which allows manufactures to maintain consistency in their processes.
Advanced biobased films are specifically designed to support the manufacture of biologics — a process that requires the product to be extremely pure and free from contamination. They can also minimise the risk of chemicals leaching into the drug product, which ensures that therapeutics are safe for patients.
AKA: How can biopharma companies optimise their large-scale cell culture workflows?
AG: To optimise large-scale cell culture workflows, commercial manufactures can adopt single-use technologies that utilise a common platform for both development and full-scale operations. They can offer consistency and scalability while allowing an end user to do real-time pilot development and scale in a common format. Often, the same family of bioreactors can be used for processes with batch volumes that scale from 5 L to more than 5000 L.
These high-performance bioreactors enable rapid scaling and intensified processing in both batch and perfusion mode, leading to higher yields while using the same — or even smaller — bioreactor volumes. Automation workflows can accommodate a variety of PAT solutions, allowing for real-time data capture as well.
Managing commercial production at larger volumes can pose a notable challenge for biomanufacturers. Single-use centrifuges can help to reduce the bottleneck that’s often encountered when harvesting sizeable batches — which is frequently associated with timely and costly depth filtration units. Such solutions can reduce material requirements significantly while also helping to eliminate 70% of waste compared with traditional harvest systems. 
Removing a proportion of the depth filters associated with current standard protocols can allow for a quicker harvesting process while minimising the yield loss that’s associated with the timely and messy depth filter flushing recovery process. Reducing the number of depth filters also positively reduces the warehousing footprint needed to store them.
Many early stage cell therapy manufacturing processes are still characterised by academic workflows, comprising a high proportion of manual steps and low expansion volumes. To pre-empt a therapy’s production at commercial scale and mitigate the potential delays associated with regulatory requirements, it becomes important to transition early stage clinical workflows to GMP-like processes as soon as possible.
From a cell culture standpoint, this often means the inclusion of bioreactors as they are scalable and easy to assimilate into closed workflows. Utilising scalable single-use technologies will be even more important as more large-scale allogeneic cell therapy manufacturing processes emerge. These will likely need to be developed in tandem with automation capabilities to fully optimise the efficiency of each process. The volumes and cell numbers associated with allogeneic manufacturing are projected to be orders of magnitude larger than their autologous counterparts; therefore, finding a single-use biotechnology processing equipment that can support this growth is crucial.
AKA: Do you have any tips for those in the biopharmaceutical industry looking to commercialise their cell or gene therapy?
AG: The success of cell and gene therapy manufacturing at commercial level is contingent on putting robust processes in place; this should happen as early in the process development period as possible. To do this, companies should engage with the appropriate regional regulatory agencies and ask them to review the process — even if it isn’t finalised. This can ensure that questions and queries are addressed early, helping to streamline the preparation and filing of INDs.
Businesses should also determine, define and develop critical process parameters and quality attributes to make sure that the appropriate assays are being developed. Furthermore, in-process and final release quality control assays should be defined, validated and streamlined early in the process development stage to reduce the impact of quality control on the price per dose.
In terms of operational and supply chain success, it’s essential to guarantee that raw materials and equipment meet global commercial manufacturing requirements. This can be confirmed by bringing in quality control and regulatory teams early on to weigh in on the process. Reaching out to vendors to enquire about their product quality, regulatory support and supply chain assurance can also be of great benefit.
Holding traceability documentation for any therapies undergoing clinical assessment is another factor that can be highly beneficial, as the necessary documents are readily available for use in regulatory board-associated applications, which can expedite the process significantly.
