John Wass, CPIP, Consultant, Commissioning Agents, Inc.
A: From a biologics perspective, with increased upstream titers having diminishing returns, downstream processing debottlenecking is getting a significant amount of attention. Chromatography is cumbersome and the technology is dated. The industry needs to see significant investment in downstream platform development. The role of filter vendors as a strategic partner in the process development stages will most likely result in a single-use disposable depth or membrane filter solution that has a media catered to a particular matrix profile. This will result in immediate significant conversion cost savings, but the real competitive advantage comes from being able to characterize and model the interactions of the product matrix with the filter media, and having the ability to predict future needs of each subsequent product in the pipeline. With an intense focus on the “speed to IND” and disproportionate number of biosimilars preparing to fill a limited number of innovator products, being able to get a product to market in 8 months instead of 10 or 12 months will become the deciding factor in growing and sustaining a competitor’s position in their respective market segment.
Christian Treitel, Pharma Business Development Head, Bosch Packaging Technology
A: In the coming years, all technological developments will focus strongly on reducing the amount of operator intervention in pharmaceutical processes and ensuring even higher final product quality. Continuous manufacturing and so-called connected industry (or industry 4.0) solutions will have a great impact on pharma processing. Industry requires technologies that minimize interfaces and streamline processes against the background of cost pressure and the need for faster time-to-market of new drugs. Process Analytic Technology (PAT) and Quality by Design (QbD) will play a more and more important role within this process to ensure that all parameters are closely monitored and final product quality is secured during development and production. Moreover, containment solutions are needed to protect operators from highly active ingredients and drugs from contact with operators.
Pär Almhem, President, Modwave
A: I think the main impact will come from integration, automation and modularization of the different process steps. We will, of course, see improvements in dosing, feeding and other unit operations, as well as analytical technologies. This is all very important and of significant value, but the main impact will come from how these systems and technologies are used as a whole, rather than from the individual components. By modularizing hardware as well as software, it will be possible to standardize and be flexible at the same time, allowing for optimization of individual components and systems, as well as adopting complete manufacturing lines to best fit the products and processes they are supporting. Proper modularization will allow for flexible, customizable systems that can be modified by switching ‘plug-and-play’ modules as needed, paving the way for reduced waste and better utilization and optimization.
Ed Godek, Manager, Process Technology, Glatt Air Techniques Inc.
A: The technologies that will have the most impact will be those that can reproducibly generate tablets for poorly flowing, low dosage APIs. Powder conditioning techniques for direct compression and good granulation technology, such as twin screw extrusion and continuous fluid bed granulation, will be required. Full characterization of these technologies will need to be done to ensure quality product. In terms of analytical technology, the old standby, NIR, will have its place in content uniformity, and its use on the tablet press will be critical. As we know, blending and mixing does not stop until the tablet is made, so we need to make sure uniformity is acceptable all the way to the feed frame of the press. We also need to develop simple methods to look at particle size and moisture. Microwave technology can be utilized for moisture content and there are several vision systems that can determine particle-size distributions of granulated materials.
Robert Dream, Technology & Regulatory Consultant, Comecer Group
A: Continuous manufacturing and integrated continuous manufacturing (ICM) have been successfully implemented at certain drug product manufacturers with the assistance of educational institutions and equipment manufacturers/suppliers. This cooperation was reached because of having the same goal and common interest in better and streamlined manufacturing. These processes, under R&D for the last several years, have been under study, and discovery is now a reality. There are some elements which are pretty obviously going to be incredibly important to the biotech industry, and some, in parts, are company secret.
With such compact manufacturing units, biotech companies could make more types of drugs, or they could quickly scale up production of blockbusters by adding units as needed. These new technologies would let firms be much more diverse and adaptive, moving in and out of different products more quickly. More flexible manufacturing could help prevent damaging drug shortages. The FDA reported 251 drugs in short supply in 2011 for medicines that are injected, as most biotech products are. About 20 percent of the time, the problem was that companies’ manufacturing capacity fell short.
The pharmaceutical industry has typically paid little attention to innovations in manufacturing, but because certain firms have kept manufacturing capacity near to their labs in Massachusetts and California, they’re now well-positioned to implement new ideas. They have the right scientists, the right engineers and the right suppliers in the U.S. We are hopeful that the U.S. will continue to be a leader in this new technology. What we are doing brings technology and innovation to the heart of the manufacturing forefront. It’s not clear how long it will take until patients receive drugs made through the new processes. At least we think that the main technical barriers have been overcome, so it’s now a business decision — this is being pushed very hard by a few manufacturers.