The Need for Innovation in Pharmaceutical Manufacturing
Investments in Single-Use/Disposable Technologies and IIoT Solutions to Capitalize on Growth Opportunities in Biopharmaceuticals
The global pharmaceutical industry is evolving with the rising need for novel therapies in the changing disease landscape. As a result of rising prevalence of chronic infectious diseases as well as growing cancer incidence, market needs are shifting from traditional small molecules (chemicals) to large molecules (biologics).
However, biopharmaceutical processing involves unique complexities in the overall process such as long running batches, batch automation and product quality which cannot be measured in real-time. To address the issues related to biopharma manufacturing, companies opt for different types of manufacturing techniques to avoid batch contamination and in turn maintain product quality, leading to the adaptive manufacturing of biopharmaceuticals.
Single use and modular technology along with a continuous processing approach is not only modernizing the industry but also minimizing the risks associated with making changes to the existing system. Single use bioreactors are being widely used in upstream biopharmaceutical manufacturing processes. Disposable technologies for downstream processes are making rapid advances, e.g. disposable, pre-packed chromatography columns. These provide seamless and scalable implementation to upstream and downstream operations in biopharmaceutical manufacturing.
Disposable production methods are generally used for lower volume manufacturing for clinical and commercial requirements. The disposable technology does not involve processes such as cleaning and sterilization of the bioreactor and hence saves time and reduces stress on the manufacturing staff. The capital expenditure is much lower compared to stainless steel bioreactor technologies but involves higher variable costs due to the need for replacement of disposable components. Key products consist of single use mixers, bag assemblers, disposable aseptic connectors, pre-packed chromatography columns etc.
The single use/disposable bioreactors enable multi-product flexible manufacturing, easy transfer of operations, fast changeover, busy facilities and lean operations. Therefore, we are witnessing a shift to flexible, small-volume manufacturing comprising of single-use systems with bio-analytical capabilities, and exploring continuous processing technologies in modular facilities.
About 40% of the total growth in the pharma market will be attributed to oncology, cell and gene therapy, rare diseases, and neurosciences.
Two multibillion-dollar biotechnology deals have already been announced in the new year resulting in the busy start to global deal making. Namely, Eli Lilly agreed to buy Loxo Oncology for about $8 billion and Bristol-Myers Squibb’s $74 billion takeover of Celgene. In early 2018, Celgene had bought Juno for a record $9 billion to boost their cancer pipeline and compete in the adoptive T-Cell (CAR-T) market with both Novartis and Gilead. In addition, there are over 400 cell and gene therapies (C>) in preclinical to phase III development, and approximately 1,700 clinical studies are underway globally.
Despite the large market opportunity, issues with product variability and a deficit in large-scale C&G therapy manufacturing capability ramain, with reported waiting time of 1.25 years before the commencement of manufacturing. Additionally, autologous therapies require special handling under very stringent temperature requirements. They are also typically time sensitive and must be delivered within clearly agreed time frames.
Biopharma companies will increasingly need to decentralize and outsource manufacturing of low volume-high complexity C> and collaborate with contract development and manufacturing organizations (CDMOs) dedicated to supporting commercialization of therapies. As more C> transition from clinical trials to commercial markets, CDMOs will increasingly employ single-use technology (SUT) in entirety or hybrid models to achieve decentralized manufacturing closer to the patient and meet challenging supply chain demands. SUT developers in turn will develop scalable solutions taking into account the challenges of extractable, leachable and reproducibility.
While 100% implementation of SUT in upstream processing will reduce the total cost of goods sold (COGS) by 15–20%, it will also reduce the initial capital outlay and net investment cost (clean-in-place, water for injection) by 35–40%. The proportion of SUT to total industry capacity is less than 10%, but new installations for C> manufacturing will witness between 25% and 30% application of SUT. Therefore, Frost & Sullivan predicts that the requirement for the commercial-scale cell and gene therapy manufacturing will propel growth in single-use technology adoption by 22% in 2019.
IIoT in Manufacturing
Over the past few years, several fundamental changes in the biopharma manufacturing process have occurred. By leveraging right first time and manufacturing 4.0 principles, the industry is looking to improve manufacturing efficiency, quality by design and compliance. Revolutionary disruption powered by an incredible shift in technologies is impacting many industries that will drive transformation in bio-manufacturing. As depicted in figure 2, all of these changes are creating a paradigm shift in pharmaceutical manufacturing to more predictive and adaptive facilities that leverage modular technology disposable components, the Industrial Internet of Things (IIoT), smart objects, remote control, and augmented reality. These techniques greatly influence design, construction, layout, and operation of a plant — and, consequently, the timing and cost of the overall project while maintaining regulatory compliance.
IIoT has the potential to transform the pharma industry by offering value propositions such as faster time to market, and cost optimization, thereby ensuring higher productivity.
IIoT also permits smart warehousing and routing of products along with predictive maintenance of machine and equipment. Benefits include lowered costs, reduction in waste production and real-time visual feedback, thereby improving operational efficiency. IIoT is expected to find application in end-to-end digital integration across the manufacturing and drug delivery value chains.
Reduce Costs, Increase Efficiency
The future of biopharma manufacturing lies in connecting data and processes, involving components of adaptive and modular manufacturing in a predictive and cognitive plant. This shall result in higher quality, efficiency, regulatory compliance and enable optimization, customization of processes and collaboration between all stakeholders involved in the manufacturing value chain. Additionally, there shall be a reduction in time to market for biologics, errors due to process variability and associated costs, thereby giving manufacturers the competitive edge to stay on the growth trajectory.
With the changing market landscape, CDMOs are adopting advanced manufacturing technologies such as single-use/disposable bioreactors, continuous, modular POD manufacturing, and so on with the integration of IT-based solutions implementing IIoT by means of strategic collaborations and partnerships. Larger participants are resorting to mergers and acquisitions (M&As) in order to gain specific therapeutic and technical expertise from smaller, niche Bio-CDMOs. As a result, CDMOs are shifting toward providing value-added services by establishing themselves as a one-stop-shop for their pharma clients.