Remedy of US’s Drug Supply Chain Shortages and Domestic Production of Generic and Brand Drugs

USA is the largest consumer of Brand and Generic drugs. Discussion here is centered around generics as they are the largest volume (84%) ⁽¹⁾ to serve the needs of US population but is very applicable to brand drugs also. Most of the US drugs are imported. Threat of US not having sufficient supply of these drugs has been there and is real. It has been talked about and discussed for quite some time. Conversations and congressional hearings ⁽²⁾ have been held. Projects ^{(3, 4, 5)} have been initiated by HHS (BARDA) and others to alleviate problem/s have no meaningful results and the problems still prevail. From my perspective all these attempts have been a charade. There is nothing meaningful on the horizon. With potential of tariffs on drugs, US needs to wake up and remedy the situation before it is too late. 

                                                               

National Academy of Sciences ⁽⁶⁾ in its most meaningless report even suggested that US should build foreign alliances to curb shortages ⁽⁷⁾. For national security reasons these recommendations ⁽⁶⁾ should have been questioned. Different US presidents have issued executive orders as far back as 2011 ^{(8, 9)} and nothing meaningful has resulted to reduce shortages or attain self-sufficiency. To bring pharma manufacturing home revamp of pharma’s business model, discussed later, along with US’s creativity and imagination is needed. This is critical. Since the industry is profitable need to change has never been a consideration. 

 

Why US has not made any progress in brining pharma manufacturing home when it can send man to the moon and bring him back. Pharma, my conjecture, has not addressed issue and/or may be does not understand the real root cause of the problem even after repeated discussions and attempts. Perspective presented is my own and is not influenced by any for profit and/or not for profit organization.  

 

Pharma companies are stuck in the current business mode (Figures 1 & 2) since middle of the last century. This is due to what I label as “equipment centricity ⁽¹⁰⁾” (Figure 1) rather than “process centricity ⁽¹¹⁾”. Since pharma has been profitable it considers itself invincible and no need to change its operating and business model has been on their radar. Figure 2 is the result of Figure1. 

Pharma’s “equipment centricity ⁽¹⁰⁾” i.e. fitting different chemistries in the same equipment has forced companies to follow stringent drug safety regulations and prescribed cGMP regimen. Downside has been low asset utilization ⁽¹²⁾. All the related costs become part of the product cost. It also has the highest hydrocarbon emissions per kilo of product ⁽¹³⁾. All of the related costs are passed on to the patients. Since the customer pays for the added costs, need for “process centricity ^{(11 )}” has not been a consideration.

With the prospect of tariffs on pharmaceuticals unless immediate steps are taken US population could suffer immensely. If US is really serious about bringing generic and brand drug manufacturing home, it has to emulate an effort like going to moon and/or create a consortium that has no outside political and regulatory meddling. Alternate business and operating model, not a rocket science, has to be adopted. Pharma manufacturing has to move from “equipment centricity ⁽¹⁰⁾” to “process centricity ⁽¹¹⁾”. If it does not this discussion will continue. 

 

Why Equipment Centricity:  

 

Why has the pharmaceutical industry dwelled on and is content with “equipment centricity”? The answer is simple. Since inception ^{(14, 15, 16)} manufacture of active pharmaceutical ingredients (API) and their formulations can be accomplished by modifying the processes to fit in the available existing equipment. This minimized new capital investment. With this pathway it accepts rigorous drug safety regulations and less than optimum use of processing equipment ⁽¹²⁾. “Equipment centricity ⁽¹⁰⁾” related costs are born by the patients.  

 

Process Centricity ⁽¹¹⁾:

 

This is not a new concept for the chemists and chemical engineers. It is pure and simple application of fundamentals of chemistry, chemical reaction engineering, processing and economics taught in our business, science and engineering curriculums ^{(14, 15, 16)} to create an excellent process. It is widely used in the fine/specialty chemical industry, older cousin of pharma. It is ironic that every reaction chemistry tells us how the “process centricity ^{(11 )}” works and how it can be exploited. Even then pharma lives in its old tradition of fitting a square plug in a round hole “equipment centricity ⁽¹⁰⁾” (Figure 1). 

 

By overlooking “process centricity ⁽¹¹⁾” especially in active pharmaceutical ingredient (API), pharma is not involving the “village” ^{(14, 15, 16)}from product inception. As a result it misses out on applying nuances of mutual and social behavior of chemicals, Sociochemicology ^{(14, 15, 16, 17)}, to create excellent processes. Some might consider this combination to be difficult. It is not. We are taught everything we need to know but have not fully capitalized on their value. We have the knowledge, creativity and imagination to accomplish the impossible. 

 

Path Forward:

 

If US wants to bring pharma manufacturing home, companies will have to internalize move from “equipment centricity” ⁽¹⁰⁾ to “process centricity” ⁽¹¹⁾. My estimate at least 180 days working 24/7 hours might be needed for each product provided it has the needed processing equipment, infrastructure, available raw materials, approved site and process. It is very possible that US might not have properly trained manpower for such task. 

 

In order for US to bring pharma manufacturing every “t” will have to be crossed and every “i’ will have be dotted. Brand and/or generics cannot be manufactured tomorrow in any available equipment . It will take time as the process and the facilities have to be approved. Processes to manufacture products just cannot be fitted in any available equipment. On top of it US does not have much of any raw materials needed for the drugs. Processing methods, equipment centric or process centric, have to be tested. Drug efficacy has to be tested. All of the above issues have to be dealt with and addressed. 

 

Companies interested in reducing/alleviating drug shortages and bringing pharma manufacturing to USA should be carrying the baton from product identification, process development, their commercialization and distribution. They have to transition from “equipment centricity” ⁽¹⁰⁾ to “process centricity” ⁽¹¹⁾ based model for the API and their formulations. Village ^{(14, 15, 16)} would have to be involved. This can happen by as stated earlier by capitalizing on mutual social behavior of chemicals ^{(14, 15, 16, 17)}, proper unit operations ⁽¹⁸⁾ and incorporating “process centricity” ⁽¹¹⁾. It will be able to accommodate variable volumes to meet patient needs in a properly designed plant. 

 

Simply said pharma’s marriage and addiction to “equipment centricity” ⁽¹⁰⁾ has been insurmountable and inseparable as significantly less effort is needed to commercialize a product. Had the chemical/pharmaceutical industry been “process centric” ⁽¹¹⁾ things would have been different. It would have had the agility to produce many different products with minimal investment. It is possible that the industry would not have gone “offshore” as USA would have led the manufacturing technology knowledge curve.   

 

CDMOs (contract development and manufacturing organization) and equipment suppliers will resist the suggested shift to “process centricity” ⁽¹¹⁾ based manufacturing. For their success they will have to support “process centricity ⁽¹¹⁾. Since CDMOs rely on “equipment centricity” ⁽¹⁰⁾ there should not be any surprise if US based CDMOs move overseas. It is time for pharma to consider alternate business model if it wants to bring pharma manufacturing to the largest market, USA. 

 

FDA will have to reconfigure itself and its approval processes for NDA (new drug application) and ANDA (abbreviated new drug application) by reducing their approval times to 90 days ⁽¹⁹⁾. Environmental and other regulatory approval times will have to be reworked. Every “K Street” ⁽²⁰⁾ residents would be an influencer. Legislators will have to participate in bringing manufacturing home by creating a FOUR STATE model and rejuvenating “Puerto Rico” ^(21,22) type model. It will be an added opportunity to bring jobs home. 

 

Companies (pharma and Pharmacy Benefit Managers (PBMs) will have to guarantee product quality and would have to accept sever penalties for any and every deviation ⁽¹⁹⁾. Companies will have to have total complete knowledge and command of the production and distribution process. Since every NDA and ANDA drug is FDA approved drug tiers ⁽²³⁾ have to go. They artificially raise prices. Direct sales to patients have to be allowed. Price, quality and drug efficacy based competition is the best way to reduce shortages. 

 

Unlike the past efforts that have resulted in nothing a collective thought through effort needs to be made. There will be resistance from every vested interest. 

 

Recent announcements by Eli Lilly ⁽²⁴⁾ $27 Billion, Johnson & Johnson ⁽²⁵⁾ $55 billion, Novo Novartis ⁽²⁶⁾ $23 billion are “equipment centric” ⁽¹⁰⁾ projects for their brand products. These are not going to be commercial at least for the next 4-5 years and will not produce products to fill tariff related immediate needs. Once patents for their drugs expire these investments could become the “white elephants” of no value looking for home.   

  

Simply said pharma’s marriage and addiction to “equipment centricity” ⁽¹⁰⁾ that has been inseparable and insurmountable needs to change. My conjecture is that “process centricity” ⁽¹¹⁾ effort will be a  “win-win” situation for the companies and a BIG win for the patients. Task is going to be challenging. US has never shrugged from any challenge. Let us be brave and get going.  

 

Girish Malhotra, PE

EPCOT International 

 

References:

1.    U.S. Pharmaceutical Statistics

2.     Woodcock, Dr. Janet: SECURING THE U.S. DRUG SUPPLY CHAIN: OVERSIGHT OF FDA’S FOREIGN INSPECTION PROGRAM December 10, 2019 

3.     Phlow Corporation Pharmaceutical Technology July 16, 2020

4.     DOD Awards $69.3 Million Contract to CONTINUUS Pharmaceuticals to Develop US-based Continuous Manufacturing Capability for Critical Medicines   January 15, 2021

5.     API Innovation Center  

6.     BUILDING RESILIENCE into the Nation’s MEDICAL PRODUCT SUPPLY CHAINS National Academies of Sciences, Engineering, and Medicine, 2022

7.     Malhotra, Girish: Has US lost its Business Acumen, Creativity and Imagination for its Healthcare Needs? Profitability through Simplicity, June 6, 2022

8.     EO 13588 Reducing Prescription Drug Shortages October 31, 2011

9.     EO 13944 Combating Public Health Emergencies and Strengthening National Security by Ensuring Essential Medicines August 6, 2020

10.   Equipment centric https://images.app.goo.gl/Qi2UZKqu4qHdLWvu6

11.   Malhotra, Girish: Process Centricity is the Key to Quality by Design, Profitability through Simplicity April 6, 2010

12.   Schrader, Ulf: McKinsey & Co. Operations can launch blockbuster in pharma, February 16, 2021

13.   Sheldon R.A. The E factor 25 years on: the rise of green chemistry and sustainability, Green Chemistry Malhotra, Girish: Active Pharmaceutical Ingredient Manufacturing: Nondestructive Creation De Gruyter May 2022 

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

15.   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

16.   Malhotra, Girish: Sociochemicology, May 30, 2013

17. McCabe W. L & Smith J. M. Unit Operations of Chemical Engineering McGraw-Hill Book Company Second Edition 1967

18.   Malhotra, Girish: ONE PAGE Road Map to Reduce Drug Shortages, Assure Quality and Improve Affordability, Profitability through Simplicity, December 6, 2019 

19.   K Street

20.   Malhotra, Girish: US’s Self Sufficiency for Generic Drugs: A Supply Dilemma and Potential Solutions, Profitability through Simplicity, March 31, 2022 

21.   MacEwan, Arthur: The Effect of 936 May 2016  

22.   Understanding Drug Tiers Accessed October 22, 2023 

23.   Eli Lilly  April 14, 2025 

24.   Johnson and Johnson April 14, 2025

25.    Novartis April 14, 2025

Sociochemicology: Redefining Chemical Process Design for Efficiency and Sustainability

In the ever-evolving landscape of fine/specialty chemical and pharmaceutical manufacturing, efficiency, sustainability, and cost-effectiveness are paramount. Traditional process design often relies on incremental optimizations, overlooking the inherent behaviors of chemicals in reaction environments. However, there exists an underutilized approach—Sociochemicology—that capitalizes on the mutual interactions of chemicals and processing equipment to drive process simplification, manufacturing innovation, and ultimately, 'Net Zero' emissions.

 

What is Sociochemicology?

 

Sociochemicology strategically harnesses the physical properties of chemicals (both used and produced), their interactions with solvents, and the processing environment to achieve efficient and sustainable manufacturing. Instead of merely scaling up lab-scale reactions into existing process equipment, this approach exploits reactant properties and equipment capabilities to enable highly efficient, near 'Net Zero' chemical synthesis.

 

Core Principles of Sociochemicology:

·       Maximizing Process Yields: Leveraging inherent chemical behavior and unit operations for efficiency.

·       Eliminating Unnecessary Steps: Understanding how reaction components influence one another to streamline processes.

·       Optimizing Equipment Utilization: Tailoring process conditions to align with the natural behavior of the chemicals.

·       Integrating Cross-Industry Equipment: Adapting machinery from other industries to enhance synthesis for APIs and fine/specialty chemicals.

 

Why is Sociochemicology Important?

 

Current chemical and pharmaceutical manufacturing methods often involve excessive complexity, leading to inefficiencies, waste, high solvent use, and elevated costs. By applying Sociochemicology, manufacturers can:

 

·       Reduce solvent usage and energy demands.

·       Enhance reaction conversion yields even in existing processes.

·       Improve sustainability by designing processes that naturally mitigate unwanted byproducts.

·       Reduce capital expenditures by developing inherently efficient processes that require fewer resources.

 

Real-World Applications:

 

While Sociochemicology is not widely recognized as a formal concept, its principles have been unknowingly employed in many successful industrial processes. By deliberately applying these principles, companies can improve existing processes and design inherently efficient, environmentally sustainable ones from the outset.

For example, in API manufacturing and fine/specialty chemicals, understanding reactant interactions can significantly reduce solvent usage and improve overall process efficiency.

 

The Path Forward:

 

Despite its potential, Sociochemicology remains largely absent from mainstream chemical engineering discourse. This needs to change. As sustainability and cost pressures mount, the industry must embrace innovative frameworks that work with the natural tendencies of chemicals rather than against them.

 

For in-depth case studies and examples, detailed discussions are available in various references (see below).

 

Join the Conversation:

This is not just a theoretical framework—it is a practical approach that can reshape manufacturing. Let’s discuss how it can apply to your processes. Reach out and join the conversation via email: girish@epcotint.com or LinkedIn.

 

Let’s challenge conventional thinking and rethink chemical manufacturing!

 

Girish Malhotra, PE
EPCOT International

 

Girish Malhotra has been advocating process simplification and efficiency in chemical and pharmaceutical manufacturing for over five decades. With hands-on experience, he developed the concept of Sociochemicology to offer a practical, efficiency-driven alternative to conventional process design.

 

References:

 

1.     Malhotra, Girish: Sociochemicology, May 30, 2013

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

3.     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

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

5.     Profitability through Simplicity

 

An Update: Artificial intelligence in Pharmaceutical/Chemical Process Development, Manufacturing & Net Zero [Post of March, 31, 2023]

In recent years talk of AI (artificial intelligence) ^(1,2) has picked up speed and progressively been touted as the methodology/technology to go to for new products, manufacturing process technology development, quality, supply chain, and inventory management etc. for the active pharmaceutical ingredients (API) and fine/specialty chemicals. When fully developed and incorporated, it is suggested and expected to be the salvation of almost every current shortcoming. I have not heard much about the use of AI based applications in the pharmaceutical products and fine specialty chemicals, if it is happening. 

 

This post is an update on my last post on the subject ⁽³⁾. There is no financial relationship with any “for profit” and non-profit” organization. We all know that API and fine/specialty chemicals are organic chemicals that have similar skeletal structures and manufacturing processes. The only difference is that one set enhance life style and the other extends/prolongs life. Many are suggesting value of AI in the new pharmaceuticals discovery and/or their manufacturing. I wonder how much of own monies has been invested or spent in R&D and manufacturing by who are suggesting the perceived/resulting benefits. Are there verifiable examples? If any of the pharmaceutical companies are exploring AI applications, they are not being discussed in open forums. 

 

Application/inclusion of AI in pharmaceuticals is possible and it can happen by taking one step at a time. Since the pharmaceutical manufacturing is regulated, my conjecture is that what all is being practiced today and is in the pipeline will not change for the brand as well as the generic drugs. Related expense is too high and no business is going to absorb it and/or pass it on to the patients. Potential application of AI to process quality and manufacturing process control is suggestive that our universities have done an inadequate job of training process designers. Every AI proposed manufacturing specific application will have to be ROI justified and tested especially if it impacts manufacturing. Regulatory approval could be a deterrent. 

 

New Product/Drug Identification: 

AI based new drug product scouting for a disease is a possibility. Someone has to pay for the effort. No one knows the time or the investment AI route will take. Time and expense for AI based effort has to be lower that the current effort. Someone will have to take a leap of faith. If it takes same as the current time and money, AI based effort will fizzle out. 

 

Product Manufacturing Process:

 

Once a potential product is suggested/selected by AI or a current method, the real task of taking the identified product to commercialization begins. If the companies stay with their current practices and methods ⁽⁴⁾ nothing will change and companies will not achieve Net ZERO ⁽⁵⁾. AI recommended methods will have to be better and economic.  

 

I thought it would be a great idea to ask ChatGPT ⁽¹⁾ what does it know about sociochemicology ^(5,6,7). It could not give any answer. On sharing a video link ⁽⁶⁾ that briefly explains sociochemicology, it was very quick to understand and share its value in development of efficient chemical processes and achieving “Net Zero ⁽⁵⁾ ” in pharmaceutical and specialty chemicals. Its search capabilities are impressive.

 

I decided to check out what AI can suggest for process chemistry and manufacturing routes for few chemicals I am very familiar with. I tested ChatGPT ⁽¹⁾ and Perplexity ⁽²⁾ by asking my credentials. “Results were interesting. They accurately identified few things but could not give details. I was told by others that AI it is constantly learning and it becomes better by answering questions. I asked additional questions and it cited some of my work.  

 

I queried ChatGPT ⁽¹⁾ about the following chemicals.

 

Saccharin:

 

I asked ChatGPT ⁽¹⁾ about the manufacture of saccharin. It gave me a process practiced by Monsanto which was abandoned in late sixties. When reminded that there is an alternate process starting with phthalic anhydride, it gave me its process details. It was significantly different and complex chemistry compared to what we practiced which was phthalic anhydride based also. It surprised me as I was involved with scale-up and manufacture of our chemistry, a continuous process that operated year round with scheduled shut downs for maintenance etc.. 

 

Omeprazole:

 

I asked about Omeprazole chemistry. ChatGPT ⁽¹⁾ does not suggest how to execute the its chemistry. Chemistry outlined in USP 7,227,024 ^(8,9) is an alternate process. Compared to ChatGPT ⁽¹⁾ suggested process ‘024 based process’s execution is very simple and can be produced using a continuous process. It includes some of the sociochemicology ^(6,7) based teachings. 

 

Metformin Hydrochloride:

 

ChatGPT ⁽¹⁾ suggests a process chemistry. It does not suggest its manufacturing process. A quick review of this chemistry suggests it can be a challenge to commercialize. An alternate chemistry and method ^{(10, 12)} suggest a safer continuous manufacturing processing. 

 

AI suggested chemistries for the above three products are not economic as better and economic processes were/are commercial. Use of sociochemicology ^(6,7) is profusely incorporated in each of the above actual and suggested processes ^(8,9,10,12) . 

 

Future Path:

 

Considering pharma’s current commercialization and manufacturing practices, about 60+ years old ^{(10, 11, 12)}, each of the following that could be AI based will have to be considered and evaluated for their economic and commercial merit. 

 

·       If the drug discovery is going to take same/similar time like the current time and path, my speculation is that all the euphoria and the related investment in AI could be lost. It can provide chemistries for the identified product but I am not sure it can generate and economic processes. This observation is based on the three chemistries I inquired about. Would AI be able to suggest the most optimum chemistry and manufacturing processes for the new molecules is not known? Even if it does, each would need a thorough review and it will have to be tested.  

 

·       For inclusion of AI each company will have to decide its commercial details e.g. business model, economics, investment, operating strategies etc.. One would expect that village’s (chemists, chemical engineers, purchasing, maintenance, accounting) journey to “net Zero” ^{(6, 12,13)} would begin when a chemical molecule is identified and/or speculated as a potential drug candidate. If a pharma company decides to fit the process in its available equipment ⁽⁴⁾, its manufacturing methods will stay 60+ years old ^{(10, 11, 12, 13)} and it will not achieve “net zero ⁽⁵⁾”. 

 

·       If companies want economic “net zero” ⁽⁵⁾ processes they will have to exploit mutual behavior of chemicals, sociochemicology ^{(6, 7)} and Real Information/Intelligence (RI) ^{(5, 6, 7, 10, 11, 12, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23)} and exploit capabilities of the processing equipment that are available and being used in other manufacturing industries ⁽⁵⁾. It is interesting to note that each process chemistry tells us about the chemicals used and produced. Their sociochemicological behavior can be capitalize on to create excellent manufacturing processes ^{(10, 11, 12, 23)}. It seems somehow pharma industry has not been capitalizing on this information. Their inclusion and consideration along with use of modular processes ^{(10, 11, 12, 23)} can deliver excellent Net Zero ⁽⁵⁾ processes.  

·       Many are suggesting application of AI for e.g. inventory control, quality control, manufacturing efficiencies, process control and supply chain etc. in pharma. It is difficult to postulate the impact of new applications. I don’t know whether if any of the AI based application suggesters have invested their own money to test their applications in pharma’s current manufacturing operations and received regulatory approval. Considering regulatory challenges this could be hard. 

If pharma companies decide to bring their manufacturing from antiquity to today and move forward, AI might be of value. However, each company will have to decide their incorporation based on cost, value and regulatory interference. Let us see where does AI lead pharma in the next two years. It would be worth re-visiting the topic.  

 

Girish Malhotra, PE

 

EPCOT International

 

1.     ChatGPT https://chatgpt.com

2.     Perplexity https://www.perplexity.ai

3.     Malhotra, Girish: Artificial intelligence in Chemical Process Development, Manufacturing & Net Zero, Profitability through Simplicity, March 31, 2023

4.     Malhotra, Girish: Square Plug In A Round Hole: Does This Scenario Exist in Pharmaceuticals? Profitability through Simplicity, August 17, 2010 

5.     Malhotra, Girish: NET ZERO for Active Pharmaceutical Ingredient & Fine/Specialty Chemicals: Nondestructive Creation, Profitability through Simplicity, November 7, 2024

6.     Malhotra, Girish: Sociochemicology , May 30, 2013

7.     Malhotra, Girish: Focus on Physical Properties To Improve Processes: Chemical Engineering, Vol. 119 No. 4 April 2012, pgs. 63-66

8.     Malhotra, Girish: Alphabet Shuffle: Moving From QbA to QbD - An Example of Continuous Processing, Pharmaceutical Processing, February 2009 pg. 12-13

9.     Malhotra, Girish: Analysis of API (Omeprazole): My perspective, Poster Session: Pharmaceutical AIChE Annual Meeting, November 11, 2009, Nashville, TN

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

11.   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

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

13.   Schrader, Ulf: McKinsey & Co. Operations can launch blockbuster in pharma, February 16, 2021

14.   Malhotra, Girish: Profitability through Simplicity

15.   Malhotra, Girish: Focus on Physical Properties To Improve Processes: Chemical Engineering, Vol. 119 No. 4 April 2012, pgs. 63-66

16.  Shreve, R. N. Unit Processes in Chemical Engineering, Industrial and Engineering Chemistry,1954, 46, 4, pg., 672, Accessed June 22, 2020. 

17.  McCabe W. L & Smith J. M. Unit Operations of Chemical Engineering McGraw-Hill Book Company Second Edition 1967 

18.  McGraw Hill Chemical engineering Series https://www.book-info.com/series/McGraw-Hill+chemical+engineering+series.mobi.htm

19.  Malhotra, Girish: Process Simplification and Net Zero: Capitalizing on Physical and Chemical Properties of Reactants and Intermediate, Profitability through Simplicity, August 20, 2024

20.  Gasteiger J.: Chemistry in Times of Artificial Intelligence ChemPhysChem 2020, 21, 2233– 2242 Accessed March 21, 2023

21.  Perry, J. H. et.al. Chemical Engineer’s Handbook Fourth Edition: McGraw-Hill Chemical Engineering Series, 1963 

22.  Levenspiel, O: Chemical Reaction Engineering, John Wiley & Sons 1999

23.  Malhotra, Girish: Process Simplification: Is the Best Answer: New Terminologies or the Application of Fundamentals? Profitability through Simplicity, December 14, 2024