Sociochemicology: Its Birth and Value

Sociochemicology ⁽¹⁾ is THINK DIFFERENT ⁽²⁾ phrase in the chemical world. Since most are not be familiar with the term and its evolution, it has its own journey. It is my journey also. It is practical inclusion of characteristics and behavior of chemicals in process design. It is not peer reviewed as there is no set charter, course or class room curriculum. Nothing new has been discovered. It is just based on how the chemicals behave with each other under the process conditions. We learn and use them to create excellent manufacturing processes. 

 

My Journey:

 

Unknown to me my SOCIOCHEMICOLOGY ^(1,3) journey started in eighth grade chemistry class. The fact that different color gases evolve when acids react with metals intrigued and fascinated me/us. I needed to see this. I coaxed fellow students to join in my project. Since we did not have glassware, we used concrete steps of the house as the test tube. We collected different acids and metal pieces and poured acids on different metals/coins to see the colors of gases produced and smelled their pungency. Experiments were a great success but were reprimanded for pitting the concrete. This w as my first experience with chemicals showing their behavior. 

 

I entered our college organic chemistry laboratory Fall of 1959 and for the first time saw lab benches with stands, round bottom flasks, magnetic and propeller agitators, condensers and beakers etc. Euphoria sank in that we are going to be experimenting with chemicals that we have been studying in the chemistry classes. Our professor gave us a tour of what is what. The fume hood and the Bunsen burners: how to lite them ON and turn them OFF etc.. It was exhilarating. Safety tips, handling of chemicals and the glassware suggested that we are going to be scientists and engineers. 

 

Our teacher’s first instruction was NEVER add water to the acid but do it the other way i.e. slowly add acid to water. Explanation was that when strong acid is added to water with inadequate mixing it generates heat and contents can boil over causing injury. Acid should be added slowly to water to absorb the heat of solution. Heat will dissipate in the water and will not boil over and cause a chemical accident by erupting water. It made sense. This was our first lesson about how the physical and chemical properties of chemicals influence and interact with each other chemical but did not fully understand this value till an incident happened in our lab. 

 

One of the fellow student must have not heard our professor or paid attention. He did exactly the opposite of what the professor had told us not to do and added water to concentrated sulfuric acid. The mix boiled out of the test tube and flew like a rocket to the ceiling and splashed over many students. Commotion set in and the lab emptied out in a hurry. No one was hurt but few days later our clothes had holes. Lesson learnt was respect chemicals, use them wisely and they can be our friend. 

 

During my sophomore chemical engineering year, our organic chemistry lab our professor gave me the responsibility to manage the laboratory, chemicals, reagents and the lab supplies. In return, I was given permission to experiment and test different synthesis routes for dyes and chemicals from our organic chemistry book. This allowed me to test reactions listed in the book and beyond as long as they were safe. This freedom allowed me to learn more than what was part of the curriculum. Unknown to me seeds of “Think Different ⁽²⁾” were planted/reinforced/strengthened/bolstered. These experiments helped me later in my career.  

 

For the last 60+ years, I have been involved in various roles in petrochemicals, fine/specialty chemicals, coatings, flavors and fragrances and other chemical industries. Roles have included reviewing chemistries, process development and design, commercialization, manufacturing, patent reviews and consulting clients at many different companies to simplify their manufacturing practices etc. This has been a continuous process. All along my career I had realized that each chemical has its unique and different behavior for each other and how we use them in our processes. 

 

With time I learnt that we can manage and manipulate physical properties to simplify processing conditions by manipulating their physical state, how and where we add these reactants to the process. This facilitated and simplified our processes. This was/is similar to social manipulation of behavior of chemicals like human behavior to create friendships and relationships, Sociology ⁽⁴⁾. So in 2013 I appropriately coined mutual behavior of chemical relationships as “SOCIOCHEMICOLOGY ⁽¹⁾. Its use has grown from benchtop experiences, experiments and application of components of triumvirate ^(3,5) to critical elements of actual commercial processes. Due to lab equipment limitations, behavior and benefits of many chemicals cannot be easily tested and/or measured easily in laboratory. However, using chemical engineering design principles, behavior of chemicals can be used in process designs and processes simplified. Without their incorporation most commercialized processes are larger version of the round bottom flask experience. 

 

We used elements of sociochemicology profusely for every batch ⁽⁶⁾ and continuous processes ⁽⁷⁾. Their inclusion allowed us to simplify processes. Some of the unit processes ⁽⁸⁾ were e.g. continuous/batch diazotization, sulfation, sulfonation, amidation, chlorination, nitration and alkylation. In addition, our processes included batch and continuous unit operations ⁽⁹⁾ e.g. decantation, filtration, crystallization and spray drying to name a few. 

 

Sociochemicology ⁽¹⁾ delivers simplicity: an ultimate sophistication and a creator‑centric philosophy.

 

Sociochemicology’s Path and Considerations:

 

We have to recognize that the process chemistry shows us the feasibility of the reaction path and process. What generally works in the lab has to be modified and fitted in the existing equipment or new equipment has to designed for the process. Final commercialized process has to be safe and economical. 

We are taught, know and have all the tools to create excellent processes but still are stuck in 80+ years old “round bottom flask” mode especially in pharmaceuticals. Why? Simple answer. We are willing to pay for inefficient processes and in the process do not care how we leave the Earth when we leave i.e. highest emissions. This is especially true for pharmaceuticals ⁽¹⁰⁾. It is up to us to challenge ourselves. If we do not, we will be stuck in the tradition of bull going around in circles⁽¹¹⁾. Food and Drug Administration (FDA)⁽¹²⁾ also has to change its ways if it/we want manufacturing technology innovation in pharmaceuticals. If a DARK HORSE using methods shared ^{(13, 14,15,16, 17)} can show how to change the landscape, there can be a domino effect. 

 

The following needs to be considered for commercial processes and the village has to be an integral part ^{(13,14,15,16, 17)}. There are other ways. There is not enough space to enumerate every option. Product volume plays a significant role in process selection, equipment sizing and use. Traditions of using what equipment is available in-house and from the vendors has to be evaluated, not an easy choice. Equipment vendors will challenge options. In addition, we have to always scout equipment that is used in other industries/applications and can be used in the chemical manufacturing. There will be considerable resistance from within the companies as well as users. These can be overcome through higher profits and better product quality.

 

We have to be always mindful in our process development/design of the fundamental fact is that every reaction happens in liquid phase. Thus, our intention has to be how to create all liquid phase. Village ^{(13,14,15,16, 17)} offers its input and expertise. Some of the considerations are enumerated. Creativity and imagination is necessary.

 

1.     Solid raw materials as a melt offer opportunities to control process stoichiometry and can reduce solvent need. Fluid flow and process temperatures can be controlled. Excess solvents facilitate the process but can become unnecessary as they occupy reactor equipment space, a prime real estate. Heat of the molten liquids speed the reaction rate.

2.     Can the solid raw material instead of dissolving in solvent can be educted in the process thereby minimizing additional solvent? This cannot be tested in the lab. 

3.     Gas can be used as liquid not only it can reduce solvent use but also can facilitate reaction rate. Gas, if added as liquid, can be used to control the reaction temperature and heat of exotherm as the liquid converts to gas. We exploited physical and chemical properties to our advantage. 

4.     Exotherms of the reactions cannot be exploited in the laboratory to facilitate and speed the reactions. Labs generally do not have the equipment or the set up to test. Ingenuity like raising the laboratory process reaction temperature comes in handy. In actual production set up using proper unit process ⁽⁸⁾ and unit operation ⁽⁹⁾, exotherms can be exploited in many ways leading to reduced solvent use, equipment size and investment. 

5.     Mutual solubilities or their lack of cannot be exploited in the lab development set up. They can be tested. However, they can be used in a commercial process to facilitate the process. There are creative ways to exploit.  

 

Unknown to our equipment vendors we used plate and frame heat exchangers (now called micro or flow reactors) and crystallizers differently. Other equipment was also used differently than the suggested use. Each company has to decide how it can capitalize on mutual behavior of chemicals i.e. sociochemicology of the reactants to have an optimum process. Overall economics has to be evaluated.  

 

We all know that without flow of liquids, centuries old practice, no reaction takes place. Since flow of fluids in lab equipment is not directly translatable to commercial equipment, what does “Flow Chemistry” really mean and what is its value. Similarly “Micro-reactors” are a fancy name for plate and frame heat exchangers that have been around and used since mid-fifties. Their use in lab development processes is not directly translatable to commercial processes. Each application and inclusion in a commercial process has to be justified. Thus suggesting “flow chemistry and micro-reactors” are new process advances in chemical and pharmaceutical manufacturing is like dressing an old house with a new coat of paint and calling it a new house, a misconception. 

 

Rational for giving new names to the traditional methods and equipment is not clear. In addition, especially micro reactors are expensive and may not fit every process. Each need has to be justified. Some of the existing commercial equipment can be used to accomplish the same objective and simplify the processes. Scale up of round bottom glassware (laboratory) to a commercial vessel (manufacturing) is not directly translational. 

 

Incorporation of the above is very possible in fine/specialty chemicals that enhance life style but not in API as the equipment/process. This is due to regulatory stranglehold and/or our inaptitude. We can practice creative designs but since the process has to be re-validated by FDA ⁽¹²⁾ after initial approval, a time consuming and expensive process each company has to share its intellectual property. No company wants to invest in better methods. Current regulatory approval methods have to change to allow incorporation of innovative processes ⁽¹³⁾. Simpler method would be that companies be allowed to proceed as long as they make sure that the product quality and performance is not compromised from the established specs. This would bring much needed manufacturing technology innovation to pharmaceuticals.

 

Process improvements and enhancements that come from inclusion of sociochemicology practices is difficult to test in the laboratory equipment. They are designed in commercial processes and are based on application of mutual social behavior of chemicals and used equipment. In addition any sociochemicology based designs being proprietary would not be published. 

 

Since FDA and other regulators are not familiar with many of the nuances of sociochemicology and if they insist on scrutinizing new and innovative methods before a drug manufacturing can be approved, no one will include and/or simplify their manufacturing processes as is the case now. From experience we included sociochemicology based designs. 

Due to limitations of the laboratory equipment, it is not easy to test mutual social behavior of the chemicals. Test of behaviors of chemicals can be a challenge but are doable if the experiments are properly designed. Creativity, imagination and knowledge of mutual behavior of the chemicals has to be included in design of such experiments. Stoichiometry i.e. the product cost and quality will be optimum. Process designed using the generated information will meet and/or exceed FDA stipulated product specifications. This would be a stark change from the current practices and the most difficult to accept and implement at the companies and FDA ⁽¹²⁾. If we want innovation in chemical/pharmaceutical manufacturing we have to be an outlier and THINK DIFFERENT ⁽²⁾. FDA’s methods have to change ⁽¹⁸⁾, a hard thing to implement and accept. 

Again to re-emphasize commercial process is judicious inclusion of the Triumvirate ⁽³⁾: unit processes ⁽⁸⁾, sociochemicology and unit operations ⁽⁹⁾. The THREE DOTS ⁽¹⁹⁾ have to be connected. So let us STAY HUNGRY and STAY FOOLISH ⁽¹⁹⁾ and “THINK DIFFERENT ⁽²⁾” thereby creating excellent manufacturing processes that are green and economical. It is best if all of the above comes internally from each company as they define and select its own pathway. 

Incorporation of TRIUMVIRATE ⁽⁵⁾ in pharmaceutical manufacturing will result in manufacturing technology innovation, significantly reduce emissions per kilo of product and that will be a game changer.  

 

Girish Malhotra, PE

 

EPCOT International

 

References:

 

1.     Malhotra, Girish: Sociochemicology

2.     Apple Think Different

3.     Malhotra, Girish: Sociochemicology: Redefining Chemical Process Design for Efficiency and Sustainability, Profitability through Simplicity

4.     Sociology

5.     Malhotra, Girish: The Process Development Triumvirate: Profitability Through Simplicity, Profitability through Simplicity

6.     Batch Process   

7.     Continuous Process

8.     Shreve, R. Norris: Unit Process in Chemical Engineering, Ind. Eng. Chem. 1954, 46,4,672

9.     Unit Operation

10.  Sheldon R.A. The E factor 25 years on: the rise of green chemistry and sustainability, Green Chemistry   

11.  Bull going around in circles  

12.  FDA

13.  Malhotra, Girish: Profitability through Simplicity

14.  Malhotra, Girish: Chemical Process Simplification: Improving Productivity and Sustainability   John Wiley & Sons, February 2011

15.  Chapter 4 “Simplified Process Development and Commercialization” in “ Quality by Design-Putting Theory into Practice” co-published by  Parenteral Drug Association and DHI Publishing© February 2011

16.  Malhotra, Girish: Report: Strategies for Improving Batch or Creating Continuous Active Pharmaceutical Ingredient (API) Manufacturing Processes, March 2017

17.  Malhotra, Girish: Active Pharmaceutical Ingredient Manufacturing: Nondestructive Creation De Gruyter April 2022

18.  Malhotra, Girish: For Domestic Pharma Manufacturing: Reorganize CDER, Profitability through Simplicity

19.  Steve Jobs Stanford Commencement Address 2005  

 

 

 

NET ZERO for Active Pharmaceutical Ingredient & Fine/Specialty Chemicals: Nondestructive Creation

Achieving NET ZERO ⁽¹⁾ has become the latest new and loud chant for the processes that produce Fine/Specialty and Active Pharmaceutical Ingredients (API). Pharmaceutical industry is known for its high emissions per kilo ⁽²⁾. Many do not want to acknowledge this. It is very possible to reduce/minimize the solvent use for every chemical synthesis process from the onset. Pathway to lower/reduce the solvent use for each product is “Nondestructive Creation” ⁽³⁾ i.e. commercialization of alternate processing method for each product from the onset. This will significantly lower the “Net Zero” number for each product from the onset ^{(4, 5, 6)} and can be applied to existing products. Creativity and imagination of everyone is welcome.  

 

It takes a whole village for an innovation to be developed, launched, and adopted.

                                                         — Edmund (Ned) Phelps, Nobel Laureate ⁽³⁾

 

Implementation of methods to achieve “Net Zero” requires effort of “THE WHOLE VILLAGE” ^{(4, 5, 6, 7)} (chemists and chemical engineers, marketing, financial analysts, supply chain professionals, quality control, regulators, maintenance, and manufacturing personnel) and has to become their religion and way of life. It is very likely that the effort might involve changes to how the chemistry is commercially practiced in the alternate equipment. Process will definitely involve reconfiguration of manufacturing/process technology and its execution. Done correctly the desired molecule and its performance will not change. I am sharing my perspective for the effort and is not influenced by any “for profit and non-profit” organization. 

 

Act of solvent reduction for every chemical process begins from the day of chemistry inception/conception as there is no tomorrow. Tomorrow never arrives as it will come tomorrow.

 

Each company can develop its own pathways. Based on my experience the simplest is to reduce the solvent use at every reaction step. That is easier said than done. It can be achieved by taking advantage of combination of physical properties e.g. melting point, boiling point and freezing point, mutual solubilities in different solvents, their mutual social behavior and chemical kinetics ⁽⁸⁾coined as sociochemicology ⁽⁹⁾. Their exploitation does simplify manufacturing processes.  

 

It is not only necessary but critical that for the long term benefit, intellectual property which involves how the processes are modified and practiced be internalized and protected at each company. Some new learning about how the unit processes ⁽¹⁰⁾ and unit operations ⁽¹¹⁾ are practiced might be necessary. Fine tuning of the existing processes/methods most likely will be necessary. For experienced chemists and chemical engineers it is very likely that the new learning to get to “Net Zero” will be minimal. 

 

It is expected and very likely that no new chemistries might have to be developed for the existing products. Current commercial  chemistries most likely will have to be executed differently in smaller/alternate equipment. In this effort interaction/mutual behavior, physical and chemical properties and reaction kinetics ⁽⁸⁾ of each chemical used and produced would have to be capitalized to simplify the processes. “Creativity and Imagination” of each member of the “THE WHOLE VILLAGE” ^{(4, 5, 6, 7)} team will be of utmost value. Process development chemist, engineer and members of the scale up team will play critical role in the effort. This will minimize implementation time. Following steps can be used to get to “Net Zero” and they are reviewed. 

 

1.     Sociochemicology ⁽⁹⁾ of chemicals

2.     Process centric designs 

3.     Creativity and imagination of the WHOLE VILLAGE ⁽³⁾

 

Each chemist and chemical engineer is familiar the above two aspects. Third is individual and collective experience dependent.  

 

Every chemical synthesis patent be, it a fine/specialty chemical or API walk us through the reaction mechanism. It is up to “The Whole Village” to harness it to create a minimum solvent use process. We are also taught all of the tools to do that unit operations ⁽¹¹⁾. Some are examples are discussed ^{(4, 5, 6, 7)}.  

 

Sociochemicology of Chemicals:

 

Sociochemicology ⁽⁹⁾ encompasses physical and chemical properties of each chemical and how they interact with each other. Mutual behavior of chemicals and processing equipment used in the process influence manufacturing methods and their execution. Each physical and chemical property needs to be exploited differently to create and simplify processes. This is emphasized as it has value for every process design.  

 

API and fine/specialty chemical industry is living with the tradition of using larger sized equipment to produce the end products. It is due to the fact that the equipment is available and can do the needed job.  

 

Round bottom flask and associated laboratory equipment does not allow exploitation of physical and chemical properties of the chemicals. Intent in the lab is to prove feasibility of the reaction chemistry. Scale up using larger available equipment is done, a tradition of SEVENTY PLUS YEARS ^{(4, 5, 6, 7)}. Laboratory does not have the provisions to experiment and demonstrate interaction of physical and chemical properties. They may be able to show feasibility but it is up to the chemist and chemical engineer “how to use them and simplify the processes”. 

 

We do not need to review the details of traditions as every chemist and chemical engineer knows them well. However, a brief of process development and commercialization would help. Generally a process engineer takes the information developed in the lab, proves its feasibility in a pilot plant and designs a process in a large reactor, a tradition of 70+ years. Since the commercial processes are “lab centric processes” and speed to market dictates commercialization, generally there is no or minimal attempt to minimize  the solvent use by evaluating and/or creating an alternate process. In pharma due to regulations after the fact does not happen. 

 

Process Centric Designs and Creativity and imagination:

 

Since most of the chemists and chemical engineers might not have the feel for the mutual behavior of chemicals ⁽⁸⁾ it can be a challenge to incorporate their nuances in actual designs. It will be necessary that due to non-availability of mutual behavior and other properties data might have to be generated internally. “Skunk works” ⁽¹²⁾ will be needed. It can be a place to experiment with alternate equipment and designs ^{(12, 13, 14)}.

 

My experience is that “process centric” designs will and do minimize solvent use. Creativity and imagination with process centric designs go hand and glove to reduce solvent use. Downsizing equipment will/should not change process chemistry but can change how the chemistry would be practiced. Such equipment is being used in chemical and other manufacturing industries ^{(12, 13, 14)}. They do lower the volume of solvent used per kilo from the current conventional agitated reactor designs. It is very possible that many could say that it cannot be done. Unless we try and consider such outlier/nondestructive creative designs ^{(4, 5, 6)}, “Net Zero” will not happen. 

 

Best is to share some examples. Most solid raw materials are generally fed in a reactor that has large excess of solvent (as much as 50%) that is used in the process. However, if the solid can be metered to the reaction system via an eductor ⁽¹²⁾ using the solvent used in the reaction, one can reduce the total solvent used in the reaction. This is especially true if a back mix flow process design ⁽¹⁵⁾ can be used. Such reaction designs along with an inline heater/heat exchanger ^{(12, 13, 14)} can reduce solvent use. Plate and frame heat exchangers ⁽¹¹⁾ have been used as reactors. It is critical that the chemists and chemical engineers have a complete understanding and command of the reaction kinetics ⁽⁸⁾. Depending on melting point and solubility of chemicals we are presented with many opportunities to reduce solvent use ^(4,5,6). 

 

As stated earlier mutual insolubilities and density differences ^{(8, 11)} can be used in many ways to facilitate and simplify processes. Some of the examples where solvent use can be significantly reduced/eliminated are reviewed ^{(4, 5, 6, 7, 16, 17, 18, 19, 20)}. There are many other examples are available in literature. One of the reasons for not incorporating many of such nuances in process design, my understanding, is the time pressure to get the product to the market. 

 

As indicated earlier almost every chemical synthesis patent shows us the pathway (reaction mechanism) to minimize solvent use i.e. direct how one can achieve “Net Zero”. Laboratory processes are fitted in the existing equipment that is available on the site, square plug in a round hole ⁽²⁰⁾. This happens as the chemical industry is tuned to using jacketed reactors for chemical synthesis, a 100 years old tradition. Most overlook how to exploit the reaction sequencing, kinetics ⁽⁸⁾ and sociochemicalogy ⁽⁹⁾  of the chemicals used and produced. Result is opportunity to lower the solvent use per kilo of the product is lost. 

 

Equipment used in other industries ^{(13, 14)} and some used differently in the chemical industry ⁽¹¹⁾ can reduce solvent use and facilitate the processes. To minimize solvent use “what if” comparison analysis is necessary to select the best equipment ^{(4, 5, 6, 12)}. At times best equipment may not be the normal agitated reactors. Inline heaters are all electric heaters and they not only minimize investment in external heat sources (boilers or hot oil heaters) but facilitate capitalizing on mutual solubilities ^{(4, 5, 6)} and reaction kinetics ⁽⁸⁾, thereby reducing solvent use for every reaction step. This value needs to capitalized on. It is time we do if we want to reduce solvent use. 

 

For example compared to conventional jacketed reactors inline electrically heated heat exchangers ⁽¹³⁾ offer much higher heat input (flux) per unit surface area (2.5 to 7.5 sq. ft./gal.) compared to conventional reactors (0.10-0.23 sq. ft./gal.). High heat input per sq. ft. improves reaction time. Their use as chemical reaction equipment is not advertised and is seldom considered. Some have and are used stealthily in the chemical synthesis for more than 60 years with excellent results ^{(4, 5, 6, 12)}. Generally they will be used in a back flow mix reactor ⁽¹⁵⁾ configuration. Most likely capital investment for electrically heated heat exchangers would lower compared to Dowtherm or hot oil based heaters.   

 

Such designs ^{(4, 5, 6)} are intellectual property of each company and need to be protected. Process designers will be challenged as at time information is not available from the vendors. They want to control their equipment use and that is tantamount to sharing proprietary information to improve their sales even when confidentiality agreements are signed. Lack of information form equipment and chemical supplier vendors has become an obstacle ⁽²¹⁾ and can interfere in “what if” analysis to select the optimum equipment for least solvent use. All factors, lack of equipment and physical properties information is and can be an interference in manufacturing technology innovation.  

 

Modular process designs ^{(4, 5, 6, 13)} can be very valuable alternate process design to current practices. They can reduce capital investment, improve profitability and add process flexibility to meet fluctuating product demands. It is possible that use of such configurations might be considered a cumbersome venture as the chemical/pharmaceutical industry is not tuned to out of the box thinking. However, we need to understand their value in reducing solvent use for every chemical synthesis process. They can be a competitive advantage and improve speed to market. 

 

Hedging on use of non-traditional equipment is an impediment to manufacturing technology innovation. All of the above are the low hanging fruits. All has to come from within each company as they know every process detail and nuance. Outsiders may be and that is big “may be” able to help but grassroot thinking has to be internal. 

 

Nondestructive Creativity Pathway:

 

Current established practice, from the laboratory to commercial scale where excess solvent per kilo is used is due to need to fit the process in an existing equipment, a case of fitting a square plug in a round hole ⁽²⁰⁾. To achieve “NET ZERO” every bit of “nondestructive creativity” and understanding of chemistry and chemical engineering by every chemical engineer and chemist will be needed and may have to be tested. They will have to think out of the box using suggested methods ^{(4, 5, 6, 7)} or any of their chosen methods. They have the creativity and imagination to excel. There will be initial apprehension but when conventional unit processes ⁽¹⁰⁾ and unit operations ⁽¹¹⁾ are applied they will see the benefits.  They could going forward become addicts. Applying out of the box ideas and concepts should not be any concern as they will be based on their education and training.

 

With all said and done underlying question would be “Is API manufacturing and fine/specialty chemicals ready to venture out to “NET ZERO”? Answer is “IT DEPNDS”. 

 

Yes there will be financial and business model implications as many of the APIs do not have sufficient product volume and can be produced on a campaign basis. Business models at companies might have to be reconfigured and there could be resistance. Upside will be significantly lower equipment idle time ⁽²²⁾ which has marred API manufacturing and can be attributed as a cause of high emissions. With alternate processes companies could respond quickly to any drug shortages. All of the above are the low hanging fruits. Again, all of the innovations have to come from within each company as they know every process detail and nuance. Outsiders may be able to help and that is big “may be”. Grassroot thinking, innovation, has to be internal.  

Since there is no mandate to achieve “Net Zero” for the existing products each company will have to justify their effort. There are financial implications for every business. They will think twice as hard to take their products to “Net Zero”. Significant amounts of monies ^{(23, 24)} are postulated to be spent from every business’s pocket with unknown return, unless there is a governmental mandate, likelihood of companies moving to solvent reduction per kilo of product i.e. REAL “Net Zero” for the existing products are extremely low. Companies could change their model as the suggested technologies and methods can lead to consolidation and higher profits. How much regulatory approval might be needed would have to be defined. Achieving “Net Zero” for the Brand and New Generics should not be a question. It is a must.  

Task at hand is not easy but if things were easy we would not have many of the technology innovations. Everything would have been done long time ago. Question going forward for us is “Are we willing and able to take up the challenge of reducing emissions?” We have a choice. Let’s make the right choice to achieve “Net Zero” in Active Pharmaceutical Ingredient & Fine/Specialty Chemical manufacturing. We owe it to the coming generations.  

Girish Malhotra, PE

 

President

 

EPCOT International

 

References:

 

1.     Net Zero: A Short history Accessed October 24, 2024

2.     Sheldon R.A. The E factor 25 years on: the rise of green chemistry and sustainability, Green Chemistry  Accessed February 17, 2021 

3.     Hubbard, G. Nondestructive Construction, TECH & INNOVATION Strategy+ Business, May 29, 2007 Accessed January 26, 2021.

4.     Malhotra, Girish: Chemical Process Simplification: Improving Productivity and Sustainability, John Wiley & Sons, February 2011 

5. Malhotra, Girish: Chapter 4 “Simplified Process Development and Commercialization” in “ Quality by Design-Putting Theory into Practice” co-published by Parenteral Drug Association and DHI Publishing© February 2011
6. Malhotra, Girish: Active Pharmaceutical Ingredient Manufacturing: Nondestructive Creation De Gruyter April 2022
7. Malhotra, Girish: Profitability through Simplicity
8. Levenspiel, O. Chemical Reaction Engineering, John Wiley & Sons Inc, 1972, Second Edition, Accessed December 20, 2020
9. Malhotra, Girish: Sociochemicology May 30, 2013 Accessed January 13, 2023
10. Shreve, R. Norris: Unit Process In Chemical Processing, Ind. Eng. Chem., 1954, 46 (4), pp. 672–672
11. Unit Operation, https://en.wikipedia.org/wiki/Unit_operation,  Accessed July 11, 2017
12. Malhotra, Girish: Quick Review of Chemicals Related Process Development, Design and Scale up Considerations, Profitability through Simplicity, November 7, 2018
13. Process Technology
14. Wattco   
15. Malhotra, Girish: Capitalizing on Mutual Behavior and Chemical Reactivity of Chemicals, Profitability through Simplicity, May 29, 2023
16. Malhotra, Girish: Review of Continuous Process for Modafinil, Continuous Processing in the Chemical and Pharmaceutical Industry II, 2009 Annual Meeting, November 10, 2009,Nashville, TN
17. Malhotra, Girish: Analysis of API (Omeprazole): My perspective, Poster Session: Pharmaceutical Engineering, 2009 AIChE Annual Meeting, November 11, 2009, Nashville, TN
18. Malhotra, Girish: Art and Science of Chemical Process Development & Manufacturing Simplification, AIChE May 17, 2023
19. Malhotra, Girish: Considerations to Simplify Organic Molecule (API) Manufacturing Processes: My perspective, Profitability through Simplicity,  April 20, 2019.
20. Malhotra, Girish: Square Plug In A Round Hole: Does This Scenario Exist Pharmaceuticals?, Profitability through Simplicity, August 17, 2010
21. Malhotra, Girish: Information Challenges for Product, Process Development and Process Design: A Reality Check, Profitability through Simplicity, April 10, 2011 
22. Schrader, Ulf: Operations can launch the next blockbuster in pharma, McKinsey & Co.,  February 21, 2021 
23. What is Net Zero? McKinsey & Company , October 25, 2024  
24. Malhotra, Girish: ENVIRONMENTAL CONSERVATION (GREEN CHEMISTRY, NET ZERO, DECARBONIZING) IN ACTIVE PHARMACEUTICAL INGREDIENTS (APIS) & FINE/SPECIALTY CHEMICAL MANUFACTURING, Profitability through Simplicity, October 2, 2024