All opinions are my own.

Tuesday, June 5, 2012

Is the New Terminology Going to Make the Pharmaceutical Processes Environmentally Friendly and Economic?

Reading two recent articles in Organic Process Research & Development magazine (1,2) had me wondering about my chemistry and chemical engineering education and practices. They created a doubt in my mind and raised a question “would the fundamentals that we had learnt and are the building blocks of the chemical industry where chemicals are either reacted or blended to produce useful products not work anymore?”

These articles also eluded that the pharmaceutical manufacturing is different and cut above the chemical industry. A new terminology rather than the fundamentals of chemical engineering and chemistry (simple heat/energy and mass balance, improving process productivity and having an economic process) are more important and necessary to design and create an economic and sustainable process. If that is the case then things have changed dramatically and many others and I could be oblivious to the change. The new terms are process mass intensity (PMI), reaction mass efficiency, E factor, Eutrophication Potential, atom economy and space-time yield etc.

During my undergraduate degree in chemical engineering, we were taught the fundamentals of heat/energy and mass balance, organic, physical and inorganic chemistry along with unit operations and unit processes, thermodynamics, chemical reaction kinetics and economics to develop processes that when commercialized using properly designed and appropriate equipment produced quality product, had minimal impact on environment and were economical. As the time progressed environmental laws encouraged us to improve processes to minimize the ecological impact.

Based on end application of the products, the manufacturing processes were labeled differently e.g. products covering surfaces were called coatings, chemicals that have disease curing value were called pharmaceuticals, chemicals that did not have disease curing value but were used as additives were classified as fine/specialty chemicals and products from crude oil were categorized as petrochemicals and so on. However, the fundamentals that were/are applied for the process design and development have not changed much.

I am not sure how many practicing chemical engineers or chemists understand what the new terminology discussed above means or are they just fancy expressions for the fundamentals that many will not understand. Due to diverse chemistries and processes of active pharmaceutical ingredients and formulations being produced in existing equipment that is not designed and/or optimized for their production, I am not sure if these factors truly on their own can deliver a green process.

There are ninety-nine references in these articles. One is from 1994 and two are from 1999. Does the lack of prior references suggest that the chemists and chemical engineers before 1990 were totally naïve and oblivious to good process development, design and engineering practices and did not use the fundamentals to develop, design and commercialize sustainable chemical processes? Or is there a latent message that the pharmaceutical development and manufacturing is elite, complex and chemistry and chemical engineering principles apply differently to them or some other principles apply?

I hope that is not the case. If it is, then it is suggests that the manufacturing will have occasional problems. This will be manifested by our lack of command of the processing steps forcing us to rely on QbA (Quality by Analysis) methods to ensure quality of active pharmaceutical ingredients and their formulations. Occasional recalls and increasing citations are suggestive of our lack of command and control of the manufacturing practices. 

To have robust, economic and sustainable processes I strongly believe that we need to have understanding and command of the processes. That can only happen by application of fundamentals that we learn in our chemistry and chemical engineering curricula along with our creativity and imagination (3,4). The products produced using such processes will produce the desired quality products. Quality by Design (QbD) will prevail and the environmental impact will be minimized. 

Girish Malhotra, PE
EPCOT International

  1. Jimenez-Gonzales, C. etal, Using the Right Green Yardstick: Why Process Mass Intensity is Used in the Pharmaceutical Industry to Drive More Sustainable Processes, Organic Process Research and Development, Org. Process Res. Dev., 2011, 15, pgs. 912–917
  2.  Jimenez-Gonzales, C. etal, Key Green Engineering Research Areas for Sustainable Manufacturing: A Perspective from Pharmaceutical and Fine Chemicals Manufacturers, Org. Process Res. Dev., 2011, 15, pgs. 900–911
  3. Malhotra, Girish: Chemical Process Simplification: Improving Productivity and Sustainability, February 2011, John Wiley & Sons Inc.
  4. Malhotra, Girish: Focus on Physical Properties To Improve Processes, Chemical Engineering, Vol. 119, No. 4, April 2012, pgs. 63-66