To assess current trends in laboratory equipment, BioPharm International turned to Francis Bach, North American sales director, Asahi Kasei TechniKrom, Inc.; Erika Lapinskas, PhD, product manager, Sartorius Stedim Biotech; Jeffrey R. Mazzeo, PhD, biopharmaceutical business director, Waters Corporation; Amber Ratcliff, product manager, analytical sensors, Hamilton Company; and Josh Silverstone, marketing director, Millipore Corp.
Q: What trends do you see in laboratory equipment for biopharmaceutical process development and quality control?
Bach: Equipment in process development labs is trending toward performing scale-up and scale-down studies to more closely resemble the exact conditions seen in the manufacturing environment.
Lapinskas: Technologies developed for bioprocess control, including process analytical technology (PAT) and product tracking (barcodes, RFID) are migrating into laboratory equipment and disposables. These offer R&D personnel similar levels of control and information from their experiments as pilot/production plant personnel have traditionally received from their processes.
Mazzeo: Adoption of PAT equipment is beginning to ramp up. Movement toward techniques that provide more detailed information about the quality of the product and changing concentration of various process components is also occurring, with techniques like LC/MS playing a lead role.
Ratcliff: Time- and cost-saving quality checks and calibrations. Technologies that allow instruments and measuring devices such as pH and dissolved oxygen sensors to be calibrated in metrology rather than in-process or in the field.
Silverstone: The long-term trend is certainly toward equipment and assays that are more rapid than those that are currently available and, ideally, can be deployed directly into the manufacturing setting.
Q: What application area is growing the fastest?
Lapinskas: Disposable and/or non-invasive sensor technology.
Silverstone: There is a tremendous interest currently in sensitive, rapid, and robust methods to detect mycoplasma and other related contaminants in biotech process streams. Also, any technology that helps speed the development and release of vaccines is of significant value to the industry.
Mazzeo: PAT, glycosylation analysis, host cell protein analysis, and analysis of nutrients such as amino acids and vitamins.
Q: What important breakthroughs have you seen in this area?
Mazzeo: While spectroscopic techniques have been successful in providing qualitative answers in a PAT environment, LC techniques, which provide quantitative information, have not been as widely adopted due to the long run times. Recent advances in fast LC methods based on higher-pressure systems and smaller particle size columns have now made it feasible to move this technology into a PAT environment.
Ratcliff: Major shifts in the integration of sensors into process controls are occurring. With advances in the ability for sensors to integrate through the use of digital industrial automation protocols, the quality and quantity of data received from measurement points is not only improving the time once required for maintenance and handling, but is also improving the associated costs. Sensors can now also communicate directly with the PLC through the generation of a 4–20 mA signal, eliminating the need for expensive transmitters and analyzers.
Silverstone: Nucleic acid-based technologies are beginning to emerge as true breakthroughs in this area.
Lapinskas: Over the past three years, there have not been significant commercial breakthroughs in this technology area. New sensors are under development for analytes including CO2 and glucose; so expanding the range of parameters that can be monitored is likely to be the next phase in this technology.
Q: What obstacles stand in the way of the development or implementation of new laboratory equipment?
Ratcliff: The onset of new technology, although in most cases better and more efficient, requires a paradigm shift throughout a laboratory and process facility. The time required for validation is significant as well.
Silverstone: Before companies can adopt new technology, they need to be confident that it can demonstrate a solid return on investment (ROI) and have a reasonably easy path to validation.
Lapinskas: Traditional monitoring systems and off-line analysis equipment are present in most upstream development laboratories. Constrained budgets may pose a hurdle to new technology adoption, particularly if the technology is disposable and the information is not available for a true cost–benefit comparison, including costs such as cleaning, recycling, energy and personnel resource utilization, etc.
Mazzeo: Regulatory acceptance and resistance to change in the manufacturing area.
Bach: Transparency to scale is still a major challenge when moving from process development to manufacturing. These departments work at different scales and use different equipment. For example, a conductivity detector in the process development lab is of a different brand and design than the one used in the pilot plant or manufacturing. This may cause variability in the results of the overall process when the two groups compare data.
Q: What is the future of laboratory equipment for biopharmaceutical process development and quality control?
Bach: True PAT Feedback and control designed-in during the process development stage is a great opportunity to move PAT further upstream in the R&D workflow. Each of these areas has the potential to move from a silo workflow and become fully integrated with overall product quality.
Lapinskas: I believe the future lab biopharmaceutical process will more accurately model the end production process. As companies continue to see process improvements and cost savings from process optimization, ensuring optimization at earlier stages of development makes economic sense. Automation and computer simulation may start to become important earlier in development.
Mazzeo: Increased use of analytical testing/PAT to support Quality by Design initiatives. Greater emphasis on information-rich methodology.