An Unconventional Analysis:

Can the Wrath of Most Favored Nation Pricing ⁽¹⁾ be Avoided by Bringing Pharmaceutical Product & Process Development and Manufacturing Practices to 21^st Century?

I have shared my learnings and experiences in process development, technology innovation, manufacturing and business practices ^{(2, 3, 4, 5, 6)}. With the looming threat of lowering the selling prices of the brand drugs through EO 14297, in this post I am sharing what are some of the things companies need to considered to avoid its wrath. Forcing brand drug sale prices by 50% or so to match e.g. European prices will have a significant impact on the P&L of every brand pharma company. However, I perceive this an opportunity for the pharmaceutical companies to lower drug prices, enhance their profits through increased affordability. Effort will simultaneously improve manufacturing technologies and reduce their environmental impact. 

 

I am not suggesting to follow and/or do what I am sharing but let your imagination and creativity take you/us to create products and processes that are our best effort. Discussion is applicable to every chemical business (fine/specialty, coatings, their younger cousin Active pharmaceutical ingredients and their formulations).  Perspective presented is mine and is not influenced by any for profit and non-profit entity.

 

My review is based on cost analysis. Our understanding of costs can assist us to improve processes and methods to enhance profits. I am not challenging any methods but suggesting that as part of continuous improvement, review of the current methods and practices for every profit and cost center can lead us to improve profits. Every little improvement is worth the effort. Readers are welcome to share their thoughts. 

 

To avoid the wrath of Executive Order EO 14297 ⁽¹⁾ pharmaceutical companies will have to review their research and development, commercialization, manufacturing and business practices. I am sure that most companies, first blush, would say it cannot be done. However, unless an ongoing concerted effort is made, the current and upcoming US Government administrations can force change of the current practices and they may not be to our liking. Litigations will ensue.  

 

US Drug Prices vs. Rest of the World:

 

For that last number of years there has been a conversation about the high brand drug prices in the United States compared to other developed and underdeveloped countries. The explanation given by the pharma companies is that price for each brand drug are the highest in their effort to recover the product development costs ($1-2 billion). Everyone has bought this explanation and believe it to be true. However, no independent body/person, has been given a verifiable explanation/justification for these costs. Prices in other developed counties are lower as their healthcare systems have been able to negotiate the sale prices. Prices in developing countries are low just for sheer volume of drugs needed. They pay for the fixed costs and keep the factories operating. Law of economics tell us that no company runs a charity and no one is going to sell their products at a loss unless we all missed the explanation/s.  

 

Proposed EO 14297, if enforced, would influence the balance sheet of every brand pharma company. In Table 1 company “X’’’s real drug, not identified, is analyzed. At this writing the world population is about 8.2 Billion ⁽⁷⁾. US population (347 million ⁽⁸⁾), is slightly less than 5% of the global population. It is interesting, just for numbers sake, to compare the sales of this hypothetical drug in USA vs. rest of the World. Numbers are estimates but are close to the numbers for a real drug. Anyone can do a similar analysis for any drug. 

 

Numbers in Table 1 tell us a story. It is logical to conclude that if the Company “X” is selling the drug at an average sale price of $0.75 per tablet in other countries and is not losing any money. This prices is less than ten percent of the US selling price. Prices ⁽⁹⁾ in other countries range from $3.00 to $0.55 per day for the 5 mg tablet. If the company has a 50% margin (this includes local pharmacist’s profits), the lowest factory cost could be ~ $0.18 per 5 mg. (based on my manufacturing and costing experience) tablet which includes the API and inert excipients. With this being the case, US selling price in a mutually subsidized healthcare system is alarmingly high. 

 

	United States	Global	Total
Population	347,000,000	8,200,000,000	8,547,000,000
Percent using (assumption)	0.42	0.42
Tablets per yr.	531,951,000	12,570,600,000	13,102,551,000
Average Price /tablet, $	9.83	0.75
Revenue, $/yr.	5,229,078,330	9,427,9500,000	14,657,028,330
Tablet, mg	5	5
API needed Kilo/year, kg	2,700	62,853	65,553

 

Table 1: Sales of a Real (unidentified) Drug ⁽⁹⁾

 

Table 1 shows the amount of API is needed to satisfy US needs vs. rest of the world. USA population’s API needs are less than 10% of the global population’s needs. Even if it was 10%, still the API volume is small. Drug for US needs can be produced at a single site. API for US demand could be imported and formulated. However, the API for rest of the world is being produced outside US and its formulation taking place at one or more sites outside USA. Without the global market, US selling price of the drugs will be higher than the current prices. 

 

Pharma companies need rest of the world market to absorb the fixed costs and maximize their profits. Claim that US brand pharma bear the cost of new drug may be right but in reality rest of the world bears significant portion of the ongoing costs and that is not well understood and/or recognized. We have to acknowledge that the US sales volume is not large enough and the sales to other countries contribute to each line item of the balance sheet and maximize every company’s profits. In other words they contribute to keep Pharma companies in business. US alone cannot be in business of inventing new drugs. Simply it is a “mutual appreciation society”.  

 

Pharma companies suggest that to develop a new drug it can take up to TWO billion dollars. These numbers to me are a hearsay as I have not been able to verify these by an “independent” entity. If EO 14297 ⁽¹⁾ is implemented i.e. reduce the selling price for this drug by 50% in USA, it can wipe out significant funding for the discovery of a “NEW DRUG”. To recoup the loss would mean that pharma will have to look at each line item of its balance sheet i.e. how to conserve. This means business model change. 

 

Pharma: What to look for?

 

Pharma companies, if EO 14297 ⁽¹⁾ is implemented most likely will have to reconfigure their business model. Every “t” and every “i” will have to be meticulously crossed and dotted for marketing, sales, product and process development, and manufacturing. It is time to shed 50+ years old business model. It needs to change as the WORLD has changed.   

 

Marketing and sales expense along with every line item will have to be reviewed. My speculation is that if a new drug for a disease is more effective than any existing drug, it will sell by word of mouth. Advertising might have to be minimized and that will be a line item savings. Let the best drugs sell based on the efficacy and performance rather than force feeding what majority of the customers do not understand. 

 

Most likely Research and Development would have to be treated as a profit center instead of a cost center. This would require each company to review their product discovery, processes development and manufacturing methods to lower their costs. “Village”^{(2, 3, 4, 5, 6)}, unlike the current tradition, would have to be involved from inception of every product development as there will be no opportunities to re-invent and optimize the drug’s manufacturing processes after the product enters clinical trials and is commercial. Effort to re-invent the manufacturing process for a brand drug i.e. under patent would be expensive as the regulators most likely would ask to reconfirm its efficacy and characteristics. 

If the above is implemented pharma landscape will change from inception. My expectation is that complete command of the product and process will reduce the regulatory approval time and lead to longer NDA “in-patent” time meaning instead of patent expiring in approximate 10-12 years might get additional 4-5 years of patent life. This could compensate lost revenue due to EO 14297’s inclusion.

 

I don’t know how many chemists and chemical engineers associated with any pharmaceutical product, process development and manufacturing are familiar with the cost analysis but it would be enlightening and of great value if the VILLAGE ^{(2, 3, 4, 5, 6)} gets involved in the product development from the start of product discovery. It is expected that some of the village members would be able to share the value of “what if” of the product development, process stoichiometry and manufacturing before a sample is submitted for clinical trials. An optimized process before it is scaled up for rigorous testing does not take time. This information can and should be used to optimize the process and minimize its environmental ill-effects. (references).

 

My conjecture is that inclusion of EO 14297 ⁽¹⁾ on pharmaceutical landscape will be beneficial to the overall pharma landscape and could reduce drug shortages and lower prices. It is best if the pharma companies took the reins and saddled the horse. Government intervention should be the last resort. Direct marketing is another option. Besides pharma companies the biggest obstacle will be the US private sector, Pharmacy Benefit Managers (PBMs) who along with their influencers will make sure EO 14297 ⁽¹⁾ it is not implemented ⁽¹²⁾. 

 

Girish Malhotra, PE

 

EPCOT International     

1.  EO 149297: Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients  

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: Research Report: Strategies for Improving Batch or Creating Continuous Active Pharmaceutical Ingredient (API) Manufacturing Processes, March 2017
5. Malhotra, Girish: Active Pharmaceutical Ingredient Manufacturing: Nondestructive Creation De Gruyter April 2022

6.   Malhotra, Girish: Profitability through Simplicity

7.   Current World Population https://www.worldometers.info/world-population/

8.   United States Population (live https://www.worldometers.info/world-population/us-population

9.   Pharmacy Checker.com  https://www.pharmacychecker.com/

10. Malhotra, Girish: Active Pharmaceutical Ingredient Manufacturing (API) and Formulation Drive to NET ZERO (Carbon Neutral)? Profitability through Simplicity, April 29, 2021

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

12.  Malhotra, Girish: Implementing Executive Orders on Domestic Production of Critical Medicines and Achieve Most Favored Nation Pricing, Profitability through Simplicity, June 11, 2025

Implementing Executive Orders on Domestic Production of Critical Medicines and Achieve Most Favored Nation Pricing

Pharmaceutical and the Drug Distribution companies have “Profitability through Sick Care” as their mission. One invents new drugs/treatments and the other distributes them. Bottom line: PROFITS are the goal and pharmaceuticals just happen to be the media. “Simplicity” in product and process development and manufacturing should always be on the forefront as they make sure that the companies are profitable. We are short on “Simplicity” aspects.  

 

Recently three EOs ^{(1, 2, 3)} were promulgated. Each has ambitious goals. However, based on the performance of the past EO’s ^{(4, 5, 6)} even after disbursing money ⁽⁷⁾ their success in delivering what is expected (domestic manufacturing and lower pricing) is highly unlikely unless methods of their execution are changed. In order to meet the objectives of the EO’s ^(1,2) fundamental changes are needed. Suggested implementation methods are reviewed. Perspective presented here is mine and is not influenced by any “for profit and non-profit” organization/s. Processes suggested in the three EO’s ^{(1,2, 3)} most likely will not lead to expected results as they do not have a total timetable. This is obvious as they suggest a time of 180 days for initial review and analysis.  

 

Without any deadlines and time line goals spelled in the EOs ^{(1, 2, 3)} a PROJECT CZAR with “accountability responsibility” has to be appointed. S/he has to be directly accountable to the President of The United States. Without such person most of the TORS ”DistribuTORS i.e. PBMs, LegislaTORS, RegulaTORS, LitigaTORS and even the produCERS and/or other unknows/knowns due to their influences and vested interests, it is very possible that these EOs ^(1,2,3) will meet the fate of earlier EOs ^{(4, 5, 6)} and will end up in a “do nothing” pile. Very bold and aggressive actions are needed for their success ^{(8, 9, 10, 11)}. As Yoda says “Do or do not. There is no try”.

 

EO 14293 ⁽¹⁾:

 

“Domestic production of critical drugs” is a noble objective. Success of this EO is dependent on fixing the current broken regulatory filing system. No one would admit that. Broken are FDA’s needed filings requirements for regulatory approvals methods and pharma’s manufacturing technologies. EO 14293 ⁽¹⁾ does not acknowledge these but this is a reality everyone knows. If everything was good there should not be any or very little back and forth between regulators and companies about the information exchange and approvals. 

 

Improvements to the existing filing and review system/methods have to be created, tested and implemented. They would be based on the information available and used in the current methods. Fallacies of the current system can be used as an example and need to be corrected. To meet the objectives EO ^{(1, 2, 3)} improvements in both, regulatory approval (FDA) and manufacture of a drug, are a must. It is my conjecture that if an attempt is made, we could bring critical and generic manufacturing home within ONE YEAR ^{(8, 9, 10, 11)}. This will require focus and effort.

 

Alternate to building a new plant/s, it is possible to repurpose existing fine/specialty chemical plants. Creative use of the available existing equipment along with process robust design not only can minimize investment, commercialization time ^{(12, 13, 14)} and but also lower total manufacturing costs. Chemical engineers are very well trained in this task. To experienced chemist and/or chemical engineer this is not difficult. On the pharma manufacturing platform chemical engineers and chemists are still fitting their processes in the existing equipment ^{(15, 16)}, an 60+ years old practice. Alternate process equipment and manufacturing process options need to be investigated ^{(12, 13,14)}. They have to be done by the process engineers and process chemists at the company sites. 

 

Improvements at FDA:

 

Results of regulatory process approval reduction time will lead to reduction in New Drug Application (NDA) and Abbreviated New Drug Application (ANDA) approval times ^(10,11). Pharmaceutical industry and US population will benefit immensely. It will lead to higher return on US Tax Payer investment through faster availability of brand and generic drugs. Every manufacturing company will benefit. Done correctly it could lead to bringing generic drug manufacturing home. FDA’s NDA and ANDA approval processes have to be equated to a “manufacturing process” where continuous improvements are needed. Without these improvements the topic of NDA and ANDA filings and their timetable will be discussed perpetually. As suggested earlier a CZAR is needed for the EO’s ^(1,2,3) to become a reality and till that happens these EO’s or like other EO of past ^(4,5,6) will not achieve their goals. 

 

In Sec. 3 EO 14293 ⁽¹⁾ acknowledges that FDA needs review of the current regulation processes. Filing  instructions (equivalent to manufacturing process instructions ⁽¹²⁾ for NDA and ANDA have to be precise and simple that any educated person can fill them and the completed application will lead to approvals in short time like 90 days from the initial filing. 

 

A quick method is suggested. If within 15 days of NDA and ANDA submission there are deficiencies, applicant should be informed. The filing company would have another 15 days to complete and re-submit the necessary information. If all of the submitted information is acceptable, the applicant should be informed and this would give USFDA another 60 days to grant and/or deny the filing ^(8,9,10,11). It is my perspective that changes at FDA’s review and approval process will also fulfill requirements of Section 9 of the EO 14293 ⁽¹⁾. 

 

In the pharmaceutical industry process development for the brand and generic drug products paths have commonalities ^(12,13,14). For commercial manufacture companies have to shed their current version of laboratory bench top or similar processes that have been practiced for the last 60+ years and practice what is science and engineering based ^{(12, 13, 14)}. Pharmaceuticals have to move from equipment centricity ^{(15, 16)} to process centricity ⁽²⁰⁾. Nothing new has to be invented. Only fundamentals of chemistry and chemical engineering need to be applied intelligently from product and process inception by the village ^{(12, 13, 14)} for the production of brand and generic products.   

 

Section 3 of EO 14293 ⁽¹⁾ mentions “emerging technologies” that enable the manufacturing of pharmaceutical products active pharmaceutical ingredients, key starting materials, and associated raw materials in the United States”. I do not know what are these “emerging technologies” as they have never been explained by US FDA citing verifiable commercial examples. Manufacturing technology development and their practices are product specific, it best to be done by the practitioners of the technology rather than being suggested by the regulators who do not have much hands on experience in their development and commercialization. 

 

It is ironic that the manufacturing processes and practices at most pharma companies are about 60+ years old bench top methods. FDA staff should be focusing on simplifying the NDA and ANDA approval methods and times rather than talking about “emerging technologies”. My conjecture is that FDA’s shortened approval time and direct marketing to patients, as explained later i.e. quicker and higher profits, will be the best incentive to develop and commercialize better technologies. Higher and quicker profits will be the result.  

 

Lately unnecessary jargon (old methods/technologies in new names; too many to name) are being introduced. Still they have to be commercialized by the companies. FDA cannot and should not coax companies to consider what companies cannot justify on commercial scale. They have the process developers, designers and manufacturing personnel who acting as the VILLAGE ^(12,13,14) can design and commercialize economic product specific processes. It is suggested that the EO 14293 ⁽¹⁾ CZAR consider options discussed ^{(8, 9, 10, 11, 12, 13, 14)} and use process designers/developers at the companies with manufacturing experience do their task.

 

Hatch-Waxman Act ⁽¹⁷⁾, it impacts the pharma landscape immensely is not mentioned in any of EOs ^(1,2,3) . It has to be revised and updated. Since the discussion here is about domestic manufacturing it is suggested that FIVE years before a patent is to expire brand company US FDA should make public every detail of approved drugs dosages, its drug performance and profile. By having the drug details companies that want to produce the generic drug will develop the best manufacturing processes, technologies that are economic. FDA approvals will also be fast. Direct sales to patients present an opportunity to manufacture the drug with the best process, highest quality at the highest profit. Every “TOR” mentioned earlier will make sure there are no changes made in the current practices and such disclosures do not happen. In reality TORs will make every attempt to swing the pendulum to tighten and extend current provisions of the Hatch-Waxman Act ⁽¹⁷⁾ in their favor. Artificial Intelligence sites ^(18,19) when asked “Does Hatch-Waxman Act ⁽¹⁷⁾ needs a change?” It suggested it is 40 years old and categorically needs revisions and simplification. 

 

Improvements at Pharmaceutical Companies:

 

Section 1 of the EO ⁽¹⁾ discusses the time it takes to build a new manufacturing facility in United States and is equally difficult to repurpose existing idle facilities to produce active pharmaceutical ingredients and formulate them. I disagree with the time suggested to repurpose a facility to produce Active pharmaceutical ingredients (API) and formulate them ^{(8, 9,10, 11)}. It is my belief that with FDA fixing its filing, permitting and approval processes (NDA and ANDA) and pharmaceutical companies following good design and engineering practices ^{(12,13, 14)} will move companies practice of fitting processes in existing equipment ^{(15, 16)} to process centricity ^(20). This may sound a daunting task but with the equipment, sometimes available at the pilot plants and idle plants, can be repurposed to accommodate most unit processes ⁽²¹⁾ and unit operations ⁽²²⁾. Out of the box thinkers and outliers are needed. They exist at every pharmaceutical company especially at their older cousin fine/specialty chemical company.  

 

It is my assumption that improvements in regulatory approval i.e. shortening the approval times for the brand companies will extend their patent’s life i.e. higher profits. Brand and generic companies will also benefit as they will have better asset utilization ^{(8, 9, 23)}. It is my expectation that real application of chemical engineering and chemistry will result in “Profitability through Simplicity”. Discussion about Good Manufacturing Practices (cGMP) ⁽²⁴⁾ are not included in the discussion as they are the corner stone of pharmaceutical manufacturing and expected to be followed.

 

EO 14297 ⁽²⁾ and EO 14273 ⁽³⁾:

  

Ways to implement EO 14293 ⁽¹⁾ has been discussed earlier. Its inclusion would be needed for implementaion of EO 14297 ⁽²⁾and EO 14273 ⁽³⁾. This going to be extremely challenging and difficult as the healthcare distributors (PBMs), their allies and every brand pharmaceutical company would come out with every INFLUENCER (TOR), explained earlier, against all three EOs. Reasons are very simple. They will have to change their business practices of the last forty plus years significant percentage of their profitability could be a stake. They may have to re-learn many things. Change is difficult. Hatch-Waxman ⁽¹⁷⁾ as discussed earlier has to be updated.  

 

Just to refresh TORS are LegislaTORS, RegulaTORS, LitigaTORS and the DistribuTORS. However if EO 14293 ⁽¹⁾ is properly implemented brand pharmaceutical companies and their TORS could and would benefit. If the distribuTORS do not change their methods to accommodate and include EO 14293 ⁽¹⁾ in there business practices, US Government has another way to force the change by letting the generics be sold directly by their producers by passing the distributors or set the sale prices so that the profits at the companies are not severely compromised. Either way PBM profits would be impacted. Change will be challenged. Federal Trade Commission (FTC) will have to establish very strict ground rules to prevent direct sale price collusion. Since profits are involved business creativity and imagination of US entrepreneurs will play a strong roll in pharma’s distribution landscape. This will be a challenging regulatory road.

 

US Government has to eliminate drug TIERS ⁽²⁵⁾, an artificial way instilled by the distribuTORS to sell same disease curing drugs at different prices. Since US FDA approves different drugs for the same disease there should not be any TIERS ⁽²⁵⁾. It would be best if these are eliminated. Let the drug price, patient and their doctor decide what is best for the patient. This along with direct sales to patients, due to their vested interests, will be resisted by the three TORS i.e. Pharmacy Benefit Managers and their allies distribuTORS, LegislaTORS and LitigaTORS. Direct sales to patients is the best option to lower drug prices. As I have indicated earlier through better technologies and manufacturing practices drug producing companies will have higher profits. This will also bring innovation in drug development, manufacturing and distribution methods.

 

Brand drug sales in USA and other countries are sold at variable prices. US prices are the highest. Explanation of high US prices is justified as recouping the product development, commercialization costs and limited patent life. This does not make sense as many drugs under patent are sold at significantly lower prices outside USA which happens to be about be less than 5% of the global population. My conjecture is that by selling brand drugs at affordable prices in most countries brand companies are recovering their fixed manufacturing costs. US Due to world’s current highest prices government has a justification for using the Most-Favored-Nation prescription drug pricing. US government will have to negotiate with the brand companies US selling prices. Brand companies and PBMs will have to negotiate sale prices and that would treading on a new turf.

 

Selling price comparison is illustrated in Table 1. 

 

Drug	Company	US Price	Overseas Price
Sovaldi	Gilead	$84,000 for 84 doses (26)	$900.00 for 84 dose India
Eliquis (2.5 mg) (27)	Pfizer/Bristol Myers	$ 9.67 per tablet	$ 0.68/ tablet (International price)

 

Table 1: Drug Price Comparison

 

Table 2 is a rough calculation of the factory cost and selling price of Eliquis. Numbers are best estimates. Cost analysis of other drugs are reviewed ^{(12, 13, 28)}.

 

Eliquis production cost
API cost, $/kilo	4,779.00 (29)
Conversion cost to tablet
Inert ingredient cost, $/kilo estimate	5,000.00
Labor cost, $ kilo	4,000.00
Factory cost, $/kilo	13,279.00
ONE KILOGRAM produces 1,000,000 tablets of ONE milligram.
Each Eliquis tablet is 2.5 milligram.  ONE kilo will produce  400,000 Eliquis tablets
Factory cost of each 2.5 mg tablet, $ = 13,279/400000 = 0.034
Profit margin 200%
Factory Selling price, $ per tablet = 0.068

 

                                                Table 2: Manufacturing Factory Cost (estimate)

 

Some of the cost numbers (ingredient and labor) used are high estimates. Even with these numbers the factory selling price is just 10% of the international price and less than ONE percent of the US price. Similar cost examples can be developed. 

 

If US Government sets the selling price to be e.g. $5.00 per 2.5 mg tablet, Pfizer/Bristol Myers Squibb are not going to like the numbers. However, to recover some of the lost dollars this gives them an opportunity to review their costs associated with R&D, Process Development, Manufacturing and others to see how they can become more efficient and recoup some of money. There will other latent advantages from developing efficient processes (high conversion yield). Similar analysis for the generic drugs illustrates the price differentials between US price and prices in India ^{(12,13, 28)}.

 

It is striking that the same drug is sold at vastly different prices ⁽²⁷⁾ outside USA. Is it a case of the pharma company’s using overseas sales to cover their fixed costs or is it a case of price negotiation or whatever they can get away with? Gilead was selling AIDs drugs at exorbitant prices in Africa till Cipla, India ⁽³⁰⁾ challenged its prices and sold the drug at $350.00 per year, an affordable price. Someone stood up to big pharma and the world benefited. 

 

Summary:

 

Recent EO’s ^(1,2,3) are suggesting that FDA, pharmaceutical companies and their distributors re-look at the landscape of the last forty years and change or the change will be made for you. The following needs to happen: 

 

1.     Review, facilitate and shorten FDA’s review and processes 

2.     Hatch-Waxman Act ⁽¹⁷⁾: Overhaul needed to minimize patent abuse leading cause of high US drug prices

3.     Repurposing using process centricity ^(20,21) is easy and has to be carefully thought through 

 

Benefits of improvements would be higher profits for the pharma companies through faster approvals, longer patent life, use of better process centric ⁽²⁰⁾ manufacturing technologies and lower pollution ⁽³¹⁾, lower drug prices, real possibility of brining manufacturing  home. However, EO’s ^(1,2,3) suggesting 180 day review essentially means nothing will happen i.e. dead on arrival. A very aggressive time table is needed for their incorporation.   

 

As discussed earlier Hatch Waxman Act ⁽¹⁷⁾ needs to be updated to the current times and is overdue. It is interesting to note that AI platforms (CHATGPT and Perplexity) ^(18,19) suggest that the loopholes to stifle generic entries have been exploited. As suggested earlier all of the performance, purity, solubility and whatever data is necessary for its generic version should be declared by the patent holding company and USFDA about FIVE years before the patent expires. Congress will have to facilitate that but many of the TORS ( mentioned earlier) have and will resist any change. Only a Presidential action can change that. However, every business specially pharmaceuticals and their allies will say “SHAME”. FDA, a tax payer funded entity, often has taken side of the pharmaceutical companies. It should refrain from doing that. Neutrality is healthy in the long run.  

Discussion with Dr. Albinus M D’Sa ⁽³²⁾ has been extremely helpful in the preparation of this perspective.  

Based on my experiences it is my conclusion that  USA can achieve the objectives of the THREE EXECUTIVE ORDERS ^(1,2,3)provided it uses the RIGHT experienced personnel. The CZAR for this project has to report to the President Of The United States. Without that kind of accountability these EO’s are not going work. Implementation and incorporation is going to be a challenge. We have the knowledge and experience of pieces and parts but need to reconfigure so that US is not paying the highest prices for the brand and generic drugs. Effort would be needed. Let us give it a go. 

Girish Malhotra, PE

 

EPCOT International 

1.     EO 14293 Regulatory Relief To Promote Domestic Production of Critical Medicines Accessed May 5, 2025

2.     EO 14297 “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients”  Accessed May 15, 2025

3.     Executive Order 14273 Lowering Drug Prices by Once Again Putting Americans First Accessed June 2, 2025

4.     Executive Order 13588 Reducing Prescription Drug Shortages, October 31, 2011

5.     Executive Order 13944 Ensuring critical medicines are made in US August 14, 2020

6.     Executive Order 14017  America’s Supply Chains Feb. 24, 2021

7.     Trump-era federal Covid contract recipient has yet to meet major deadlines Accessed May 17, 2025

8.     Malhotra, Girish: An Outlier Plan to Bring Pharmaceutical Manufacturing to USA in One Year

Profitability through Simplicity April 28, 2025

9.     Malhotra, Girish: Remedy of US’s Drug Supply Chain Shortages and Domestic Production of Generic and Brand Drugs Profitability through Simplicity, April 15, 2025

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

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

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

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

14.  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

15.  Malhotra, Girish: Why Fitting a Square Plug in a Round hole is Profitable for Pharma and Most Likely Will Stay? Profitability through Simplicity August 1, 2014

16.  Equipment centricity

17.  Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act) 

18.  ChatGPT.com

19.  Perplexity.ai  

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

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

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

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

24.  cGMP Practices

25.  Understanding Drug Tiers

26.  Washington Post December 1, 2015

27.  Pharmacychecker.com Accessed June 1, 2025

28.  Profitability through Simplicity

29.  Eliquis API price https://www.pharmacompass.com/active-pharmaceutical-ingredients/eliquis  June 1, 2025 

30.  Indian Company Offers to Supply AIDS Drugs at Low Cost in Africa February 7, 2001

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

32. Dr. Albinus M. D’Sa