Welcome to the ninth in a series of AIChE blog posts profiling process engineers, a diverse group of professionals spanning multiple industries and regions. In this series, we aim to profile process engineers who work in fields as diverse as petrochemicals, pharma, bulk chemicals, food, and any process-intensive industry.
Are you a member and process engineer interested in being profiled? We'd love to hear from you via this volunteer opportunity. Also, we hope to build an online discussion group specifically for process engineers. You can find out about both of these initiatives and join our efforts by visiting https://www.aiche.org/processengineering
For our ninth profile, we meet process engineer Ecevit Bilgili. He talks about beginning his career as a process engineer developing and manufacturing drug products for Merck & Co., Inc., and the transition to his current role as an associate professor at NJIT. He also discusses overcoming specific challenges, and the importance of his work.
Tell us a bit about your work as a process engineer.
While I was looking for an academic post during my postdoc at University of Florida, a senior chemical engineer position opened up at the West Point facility of Merck & Co., Inc., which attracted my attention.
My postdoc advisor informed me that Merck was a great company to work for following a postdoc, as well as a great place to continue my research and development efforts. I took his advice to heart and started an industry career there.
As a process engineer, I worked on the development and manufacturing of drug products like tablets. Developing a drug product is a sophisticated, complex, multi- and interdisciplinary endeavor. From the discovery of therapeutically effective molecules to the manufacturing of final drug products intended to cure diseases, the process is quite involved.
In my relatively short industry career from 2004-2009, I was involved in the development of processes for a blockbuster drug and several other drug products. During this time, I also served as a technical expert on mixing, milling, and fluidized bed technology. My job entailed developing pharmaceutical unit operations and their scale-up to manufacturing facilities in and outside the mainland U.S. I performed these roles while also supporting external manufacturing operations.
Fast, streamlined development of pharmaceutical products is beneficial to companies for greater market penetration and dominance. It also helps patients suffering from life-threatening diseases like cancer and AIDS to receive medication faster, which in return, saves millions of lives.
Specifically, I performed batch fluidized bed granulation experiments at a kilo-scale (lab scale) and developed the process which scaled up to a few hundred kilograms at the manufacturing scale. The job also entailed performing and supporting all technical and scientific work that defined the final market image of the drug product, ensuring the physico-chemical stability and adequate shelf stability and also assuring the therapeutic efficacy. This supported the filing with various regulatory agencies like the Food and Drug Administration (FDA) and European Medicines Agency (EMA).
After my process engineering experience at Merck, I took an assistant professor position at New Jersey Institute of Technology (NJIT) in 2009. Since then, my Particle Engineering and Pharmaceutical Nanotechnology Lab (PEPNAL) has been conducting research in designing particulate formulations and processes for high-value-added products. These products include pharmaceuticals with enhanced functionalities, including bioavailability enhancement of poorly water-soluble drugs.
In my current job as an associate professor, I continue the practice of process engineering and develop robust, integrated, and intensified processes for the production of drug nanoparticles and drug-laden nanocomposites.
Why did you become a process engineer?
At the end of my freshman year, the chemical engineering department of Bogazici University (Istanbul, Turkey) arranged a plant tour to PETKIM’s petrochemical refinery and Pirelli Tire Plant in Izmit, Turkey. The sheer size of the plant and enormous scale of processing equipment at the refinery both impressed me and stirred up excitement about developing and designing processes.
A summer internship at Swiss-based Roche Pharmaceuticals in Istanbul allowed me to work in a chemical synthesis plant, where I learned how a chemical plant works for the production of an active pharmaceutical ingredient. I was also exposed, for the first time, to the practical aspects of integration of chemical reactors, unit operations, and process intensification via reactive distillation.
This experience evoked curiosity and led to my interest in the pharmaceutical industry. To this day, I have continued to interact with the pharmaceutical industry and will continue doing so throughout my career.
What are some of the biggest challenges you face in your role as a process engineer?
Process engineers in the pharmaceutical industry usually perform both product design and process design simultaneously late in Phase II of clinical development up to the marketing stage of the product. Due to competition with branded and generic pharmaceutical companies, pharmaceutical companies must develop the product and associated processes fast. The goal is to reach the market first, while ensuring the purity, safety, and efficacy of the product, meeting all regulatory agencies’ and payors’ requirements. Achieving compliance and acceptance by both patients and doctors is also very critical.
Process development and scale-up in such a fast-paced, demanding, and regulated environment requires process engineers to make the best use of wide-ranging tools and skills to minimize development time, resources, and cost.
These tools include the principles and fundamentals of chemical engineering and pharmaceutical sciences, scale-up rules, computational modeling, project management and operational excellence tools such as Six Sigma, retrospective reviews of prior development experiences, and prior in-house and external knowledge base.
A particular challenge for process engineers working with particulate materials such as powders, which are commonly used in the pharmaceutical industry, is that such materials often exhibit complex, non-intuitive behavior that cannot be easily explained by traditional constitutive equations (thermodynamic equations of states, rate laws, etc.) valid for solids, liquids, and gases.
While much academic progress has been made in this field, relating this knowledge to industry practices is lagging behind. This is partly due to the fact that none of the undergraduate curricula of engineering disciplines, including chemical engineering, cover particulate materials–processes adequately (unlike their coverage of liquids and gases).
Hence, in the absence of such formal training on particulate materials, process engineers in the pharmaceutical industry have mainly relied on empiricism and trial-and-error approaches historically. However, with the FDA’s recent Quality by Design (QbD) initiative, there is a greater emphasis on advanced processes, product understanding and building quality into products by design. This has led to more extensive use of scientific–engineering principles, process modeling, statistically-based design of experiments, and process analytical technology (PAT) in development and manufacturing of drug products.
How is your work as a process engineer critical to your particular job assignment or industry?
Process engineers play a vital role in the manufacturing of safe, efficacious drug products and allow patients world-wide to benefit from molecular therapeutics discovered in minute quantities.
Without large-scale manufacturing or in case of drug shortages, millions of patients would not have access to therapeutic drugs. By consequence, they would suffer from the lack of availability.
Fast, streamlined development of pharmaceutical products is beneficial to companies for greater market penetration and dominance. It also helps patients suffering from life threatening diseases like cancer and AIDS to receive medication faster, which in return, saves millions of lives.
With increased pressure from payors (government agencies and insurance companies) as well as the demand for lower drug prices, it is becoming more and more important to reduce manufacturing costs. This is accomplished through cost-effective manufacturing processes as well as a paradigm shift from batch to continuous manufacturing.
Process engineers will continue to play a major role in this endeavor in the pharmaceutical industry.
What do you think is most important about what you do as a process engineer?
While I always felt having an excellent chemical engineering background and skills is at the core of my job, that is not the only skill of importance.
Process engineers need to combine scientific–engineering principles with experience and equipment/operational know-how along with project management skills.
Another absolute necessity is to have effective communication and team skills. This is important because all projects require process engineers to work with scientists, engineers from other fields, and people with potentially non-STEM or non-engineering backgrounds. This encompasses those involved in quality–cGMP, regulatory affairs, marketing, and supply chain.
How has your practical experience as a process engineer translated into your academic experience?
When I started at NJIT as an assistant professor, the first course I taught was an undergraduate course titled “Separation Processes II." It focused on some of the contemporary separation processes such as membranes, adsorption, chromatography as well as traditional separations such as crystallization and drying.
I began teaching examples, failure–success stories, industrial applications, and industrial practice which was partly based on my process engineering experience. This certainly enhanced students’ engagement, motivation, and interest.
Even in other courses I taught, such as “Fluid Flow” and “Transport Phenomena,” I have always found ways to share my industrial experience and common industrial practices with my students.
Both official and unofficial student feedback indicated that the incorporation of “industry perspective” into teaching was an important highlight of all of the above courses I taught; and student evaluations were extremely favorable and encouraging.
As I mentioned before, my research involves various elements of process engineering. Using process intensification concepts, we have recently demonstrated the production of dense drug suspensions with sub-100 nm particles, which can be easily scaled-up and used in industry.
Similarly, we are using a multitude of modeling approaches such as population balances, CFD, microhydrodynamic models, and discrete element modeling for better understanding and optimizing various particulate processes. These processes include but aren't limited to milling and fluidized bed granulation.
Also, my past process engineering experience has allowed me to produce engineering solutions that could potentially have a significant industry impact. Because of this, there's no surprise that my research has been largely funded by companies such as Boehringer-Ingelheim, Catalent Pharma Solutions, SCG Thailand, Nisso, International Flavors and Fragrances, as well as FDA/NIH and NSF ERC for Structured Organic Particulate Systems.