A: I see the biggest impacts enabling scale-up and commercialization of next-generation therapies in the near term as small tweaks on existing platforms: items like incremental advances in closure of single-use systems enabling a completely closed cell therapy process, improvements in plastics creating more robust integrity at cryogenic temperatures, or working out nuances of adapting isolator technology to operations requiring a high level of dexterity and high turnover. Automated robotic systems have great potential but are still not having the impact of simpler automated devices that combine peristaltic pumps and pinch valves. The next-generation antibodies (e.g., Fabs, bispecifics) could be made with the same process trains as mAbs, but continuous processing will enable them to reach commercialization with less capital investment.
A: Next-generation processing is quickly gaining traction in the industry because of the significant impact it will have on bringing therapies to patients. This manufacturing evolution will intensify the manufacturing process from multiple unit operations to a continuous flow-through process.
At MilliporeSigma, we start process intensification by updating and upgrading outdated unit operations, then connecting these processes to run in a continuous flow-through fashion and ultimately reaching what we call “contiGuous” manufacturing — that is, a process that is continuous, connected and digitally enabled with all the suitable software and automation, run as an orchestrated production train. However, while continuous processing is the future of drug manufacturing, customers face challenges today in terms of speed to market, facility flexibility or cost of goods. We’ve designed the BioContinuum™ Platform to feature next-generation technologies that provide incremental process benefits now, with a mind to the “contiGuous” process of the future. The platform will revolutionize drug manufacturing by setting the standard for improvements in process efficiency, simplified plant operations and consistency in manufacturing. We predict that by 2020, approximately 20 percent of today’s molecular pipeline will be manufactured using elements of next-generation bioprocessing, or “contiGuous” manufacturing.
A: It is important to discuss two key areas in manufacturing science that are developing in the pharmaceutical industry. The first is not necessarily scale-up, but rather streamlining manufacturing by pushing pharmaceutical manufacturing into the 21st century.
For example, continuous manufacturing processes utilizing engineering techniques long used by other industries. Unlike what was once exclusively a batch process, with a multitude of limitations (inefficiencies, higher costs, higher risks of failed batches), drugs may now be produced in continuous manufacturing lines, coupled with precise monitoring through technologies like PAT (process analytical technology). It is important to note that a paradigm shift in manufacturing technology such as this will require manufacturers and suppliers to work side-by-side to design safe and effective processes.
Next, instead of scale-up, next-generation therapies are likely to be scaled down, as a result of the personalization of medicine. We are not far off from walking into a local pharmacy and having a precise dosage form tailored to an individual patient, whether it is a 100-kg adult or a 2-year-old child. One such example would be the use of a 3D printer, mixing APIs and excipients as liquids, solids or melts to form exact dosage forms essentially on demand.
A: Manufacturing across many industries, including pharma, is evolving into more digital, automated environments. As this occurs, the use of artificial intelligence (AI) to optimize the manufacturing environment, including better predictive tools for instrument performance and maintenance, could provide pharma with significant efficiency gains in productivity and is a compelling technological advancement in manufacturing.
AI could also be deployed to optimize complex manufacturing lines, including biologics where process monitoring and feedback will determine the final product quality characteristics and can ultimately provide faster scale-up. Additionally, adoption of the Internet of Things (IoT) into manufacturing will also provide the industry with tighter, real-time controls, accelerating scale-up and release testing for small molecule and biologics manufacturing.
A: A large number of next-generation therapies are personalized drugs and formulations, which target smaller patient groups. Consequently, they are typically produced in small batches, which requires manufacturers to turn toward flexible manufacturing operations. This is where ready-to-use (RTU) containers come into play, and more specifically, standardized platform solutions. By working closely with pharma companies, machine manufacturers, and elastomer component suppliers, we introduced our iQ™ platform, which standardizes the tub format of RTU syringes, vials and cartridges to allow the different containers to run on the same filling line. Due to the standardization, fewer change parts are necessary when switching from one container to another, enabling pharma companies to fill various drug/container configurations on the same line with minimized changeover times. This enables the short time to scale-up and commercialization of these drugs.
A: Purpose-built technologies are developed to meet next-generation therapy process requirements both today and in the future.
Automation is enabling robust, consistent and connected manufacturing, eliminating significant risk from manual and open processes. Complete integrated process workflows, such as the GE FlexFactory for cell therapy, enable therapy innovators to rapidly create the manufacturing capacity needed for both clinical and commercial production.
A: The cost of manufacturing biologics is among the highest for total investment within the market segment. Drug substance manufacturing, in particular, is labor-intensive and time-consuming due to sensitivity to environmental changes, inconsistent yield and low purity. Because the basis of manufacturing involves living cells, any opportunity to streamline proliferation and purification via continuous processing or real-time monitoring will prove highly impactful for scale-up and commercialization of biotherapeutics.
Erich is an industry SME in bioprocess and has over ten years of experience in the pharmaceutical and biotechnology industries. He specializes in leading process-intense conceptual designs and engineering of biotech and aseptic processes with facilitation through detail design and construction. His years of simulation and operations research knowledge, and small-scale biochemical engineering methods, bridges the design gap between true R&D and full-scale production. He helps biopharmaceutical clients deal with higher titers in existing facilities and designs new cell therapy facilities.