FDA’s ANDA Prioritization Pilot and Possibilities of its Success

 

On October 3, 2025 CDER FDA ⁽¹⁾ announced “New ANDA (abbreviated new drug application) Prioritization Pilot to Support U.S. Generic Drug Manufacturing and Testing” ⁽²⁾ process it would like to experiment with in its efforts to bring generic manufacturing home to USA. 

FDA has ignored the need for US manufacturing and not done anything even after numerous testimonies in front of US Congress by various responsible FDA personnel and US Presidential Executive orders ⁽³⁾. The recent proposal/experiment ⁽¹⁾ to bring generic drug manufacturing home is due to considerable pressure from the current US Administration. 

 

Following is part of FDA’s acknowledgement ⁽¹⁾ and proposal to bring generic drugs manufacturing home.  

 

Overreliance on foreign drug manufacturing and testing creates risks both to national security and patient access, and undermines investments in U.S. research, manufacturing and production,” said Dr. George Tidmarsh, M.D., Ph.D., Director of FDA’s Center for Drug Evaluation and Research. “It also slows down reviews and costs taxpayers more money, as these foreign research and testing sites must be inspected by FDA, and foreign inspections take more time to prepare for and are more expensive to conduct than domestic inspections ⁽²⁾.

 

The proposed process is flawed, in my estimation, as it has not been thought through and has significant limitations. Perspective presented is my own and not influenced for any outside influencers. 

 

Several proposals to bring generic drug manufacturing home have been proposed ^(3,4,5,6,7) and all have been shared with CDER ⁽¹⁾. Without a 90 day roadmap (4) FDA’s current effort will go no where. 

 

In the current proposal ⁽²⁾ it seems that that every ‘t” has been not crossed and every “i” has not been dotted. It relies on an old FDA proposal ⁽⁸⁾. Was this ever tested? If it was successful why it was not implemented. 

 

Under the current proposal ⁽¹⁾ for the companies to apply for FDA’s consideration they have to meet the following requirements. 

 

1.   ANDA applicants have to conduct the required bioequivalence testing in the United States. 

Does FDA have a list of companies that are in the public domain and is their testing acceptable to US FDA? Is the list in public domain? Would FDA accept bioequivalence test results from the US based companies and have they been approved? What is their track record? 

2.   One of the requirements for the priority review ⁽²⁾ is that “company’s products are made in the U.S. using exclusively domestic sources for APIs.” This would mean raw materials and equipment.

Have the authors and proposers of the guidelines ⁽²⁾ checked the availability of raw materials in USA? Does FDA know and understand that majority of the raw materials are not available in USA? Has FDA thought through the raw material availability limitation? This will result in very few, if any, companies to qualify for “priority review submission”. There are and/or gaping deficiencies in the proposed path ⁽²⁾. Even ONE success should not be considered a total success. US has long ways to go before it can call bringing generic drug manufacturing home. 

With that being the case how many companies will qualify and would be able to fulfill the basic requirements of the new proposal ⁽²⁾. Based on nonavailability of US raw materials FDA’s ANDA Prioritization Pilot ⁽²⁾ is destined to failure and possibilities of its success are close to zero on a scale of one to ten. Is this proposal just a window dressing to show the current administration, US Congress and public at large that it is doing something to bring generic drug manufacturing home.  

3.   The new Pilot ANDA ⁽¹⁾ is based on a program that was proposed by FDA ⁽⁸⁾ in 2006. Was that program ever tested ⁽⁸⁾and/or adopted by FDA and or any pharmaceutical company? What are the results? I do not know its success or it has been sitting on the shelves and gathering dust. HAs it been brushed and/or tested/ updated for its validity and applicability to meet 2025 economic and political needs. Are there any case successes? 

It seems the current proposal is being suggested under duress and the new proposal ⁽²⁾ is just a trial balloon destined for failure? 

US FDA needs to address the doubts cast above and will be cast by many. Another question FDA needs to address is “does it have sufficiently experienced personnel who have prepared the latest proposal and have walked such a talk”. Answers to the above questions will be very interesting. I am sure there are additional questions from others.  

 

Girish Malhotra, PE

 

EPCOT International

 

References:

 

1.     CDER  

2.     New ANDA Prioritization Pilot to Support U.S. Generic Drug Manufacturing and Testing FDA.gov October 3, 2025

3.     Malhotra, Girish: Profitability through Simplicity

4.     Malhotra, Girish: ANDA (Abbreviated New Drug Application) / NDA (New Drug Applications) Filing Simplification: Road Maps are a Must. Profitability through Simplicity, May 11, 2017 

5.     Malhotra, Girish: Simplified Roadmap for ANDA/NDA Submission and Approval will change Pharma Landscape, Profitability through Simplicity, November 25, 2018

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

7.     Malhotra, Girish: What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days? Profitability through Simplicity October 24, 2025

8.     Prioritization MAPP  CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5240.3 Rev. 6

 

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