How Systems Engineering Could Improve Drug Development

Efficiency is a key goal in all aspects of pharmaceutical development—from initial synthesis, to clinical trials, to manufacture—and employing engineering concepts may greatly improve it.

Engineering and pharmaceutical science are related disciplines. Both use models to predict outcomes and enhance efficiencies of product manufacturing and use. These principles can also be applied to drug development, from preclinical trials up to production.

Recently, there has been interest in incorporating systems engineering into pharmaceutical development and manufacture. Systems engineering is focused on an interdisciplinary approach to ensure all processes involved in product development are harmonious and efficient. Often, the goal of systems engineering is to design systems (interdependent “parts”) that work together to ensure consistent, high-quality product is produced with the upmost efficiency.

Systems engineering is often discussed in the realm of commercial product development, but recently, it has been discussed in pharmaceutical circles to optimize various aspects of drug development and manufacture. This is especially true with respect to pharmaceutical manufacturing processes.¹

Current manufacturing processes can consume a significant amount of revenue from the company producing the drug² and spur many issues that increase cost. Traditional batch processes can have quality control issues, leading to manufacturing waste, delays, and recalls.³ Some are calling for a systems engineering approach that involves integrating continuous manufacturing processes and replacing scaled-up batch processes. This is called continuous pharmaceutical processing, which is mostly focused on small-molecule drug production, but can also be applied to biologics.⁴

Integration of continuous pharmaceutical processing has the potential to allow for more economical process line shutdown and initiation, accurate tracing of material throughout the production cycle, and enhanced quality in the presence of alterations in the processing line. All of this would increase the quality of the end pharmaceutical products produced and increase production efficiency.

To accomplish this, systems engineers and pharmaceutical scientists are beginning to propose modeling manufacturing systems and using enhanced control technologies.^4,5 Revamping current manufacturing processes, modeling continuous pharmaceutical processing, and developing control systems that can integrate the different steps in the manufacturing process will require significant investment.

Because these developments have the potential to benefit the pharmaceutical industry as a whole in the long term, some have suggested increased joint funding of research in this area. Specifically, enhanced funding of and collaboration with research universities may aid in the development of novel manufacturing approaches in the pharmaceutical industry.⁴

Systems engineering can be applied to other aspects of pharmaceutical development, including modeling approaches to predict new drugs’ preclinical and clinical pharmacokinetics (PK) and pharmacodynamics (PD). Physiologically-based PK is an example of such systems modelling, which assigns PK parameters based on physiological measurements to more accurately predict drug disposition.⁶ The principles of systems engineering, controlling the multiple factors that can impact PK/PD in the preclinical stage, may allow for better prediction of drug disposition, better initial dosing prediction, smoother transition into clinical trials, and reduced late-stage attrition rates.

For now, enhanced efficiency of pharmaceutical processing has the potential to benefit all parties involved. Pharmacists and pharmaceutical scientists can incorporate a multidisciplinary approach to improve drug development and manufacture. Enhancing efficiency and reducing cost at any stage of drug development is in the best interest of companies and consumers alike, and systems engineering has the potential to make it happen.

References

1. Rogers A. Process systems engineering methods for the development of continuous pharmaceutical manufacturing processes. rucore.libraries.rutgers.edu/rutgers-lib/47570. Published 2015.

2. Basu P, et al. Analysis of manufacturing costs in pharmaceutical companies. J Pharm Innov. 2008;3(1):30-40.

3. Buchholz S. Future manufacturing approaches in the chemical and pharmaceutical industry. Chemical Engineering and Processing: Process Intensification. 2010;49(10):993-995.

4. Myerson AS, et al. Control systems engineering in continuous pharmaceutical manufacturing. May 20—21, 2014 Continuous Manufacturing Symposium. J Pharm Sci. 2015;104(3):832-839.

5. Troup GM, Georgakis C. Process systems engineering tools in the pharmaceutical industry. Computers & Chemical Engineering. 2013;51:157-171.

6. Jusko WJ. Moving from basic toward systems pharmacodynamic models. J Pharm Sci. 2013;102(9):2930-2940.