For Domestic Pharma Manufacturing: Reorganize CDER

For more than two decades US Government has been aware of potential political and strategic supply chain issues related to availability of the generic drugs. Many congressional hearings have been held on the subject (too many references to cite) that have not led to domestic supply of the generic drugs. Multiple Executive orders ^{(2, 3)} have been issued by various US Presidents that have not resulted in any progress in addressing the issue related to drug shortages and bringing pharma manufacturing home. Department of Health and Human Services (HHS) ⁽⁴⁾ along with US Food and Drug Administration’s ⁽¹⁾ management hierarchy have been and are very aware of dire possibility of US being held a drug supply hostage but have ignored and not proposed any path or plan to make sure that the generic drugs can be sourced domestically. It is well known that US’s greater than 80% of the generic drugs are sourced from India and China.  

            

With no progress on the issue, US can be held hostage for its healthcare needs. Yes HHS ⁽⁴⁾ has doled out monies to many entities to come up with plans to reduce shortages or bring manufacturing home. Most prominent being PHLOW Corp.⁽⁵⁾ and many others to figure out methods and plans to alleviate potential drug shortages. However, the projects have been meaningless and have yet to deliver any positive results. Had they been successful, HHS ⁽³⁾ would have bellowed its horn/s. 

 

Since CDER, Center for Drug Evaluation & Research ⁽⁶⁾ at FDA ⁽¹⁾ is responsible for approving the brand and generic drugs, responsibility of making sure shortages do not happen and the supplies are not curtailed, it has to make sure there is a plan. If there is or was a plan it has not been presented to the US Congress and/or Legislators or is in public domain. 

 

Since HHS ⁽⁴⁾ and US FDA’s ⁽¹⁾ management hierarchies have ignored and not proposed any viable path or plan to obviate this potential national security threat, a plan to assure continuous supply of US produced generic drugs is presented. Route and views presented are my own and not influenced by any profit making and non-profit organization. It is based on my sixty plus years of experience in business and manufacturing management, process development, product commercialization, strategic and intellectual property management where the mission has been “Profitability through Simplicity” ⁽⁷⁾. Presented plan has been discussed with former regulators and they have been enthusiastic about my proposal.  

 

FDA’s ⁽¹⁾ ANDA ⁽⁸⁾ Filing and Approval Process:

FDA ⁽¹⁾ publishes a yearly activity report ⁽⁹⁾ for the generic drugs. It is complex and only well-versed can understand it. It does not tell exactly how many applications were filed in any fiscal year and how many of those filed in the fiscal year were approved. 

 

Going forward the generic drug ⁽⁸⁾ approval pathway, that will bring their manufacturing home has to be simple. To achieve returns that are acceptable to any investor, CDER ⁽⁶⁾ has to create the landscape that would attract investment. At this point I do not believe there is any. In its effort FDA ⁽¹⁾ recently announced NEW Priority Pilot ⁽¹⁰⁾ has to be carefully reviewed. Irony is that this is rehash of a plan proposed in 2006 ⁽¹¹⁾ which obviously did not and has not improved filing processes and/or brought any generic manufacturing home. I wonder if its value or purpose has been understood. It seems more to be a legal document rather than a road map that can be readily used. 

 

Proposed Plan:

Under the proposed plan CDER ⁽⁶⁾ where brand NDA ⁽¹³⁾ and generic ANDA ⁽⁸⁾ drugs applications are reviewed has to be split in two distinct groups. Discussion here is focused on generic drugs and its experience and time lines can be adopted by the brand ⁽¹³⁾ team also. Each group would perform as a business unit with their performance being measured on the basis of filled and approved generic and brand applications. Under the proposed plan if the approval time for the generic drugs ANDA ⁽⁸⁾ exceed three months ⁽¹²⁾, their review and approval processes need to be changed and simplified to meet the three months approval requirement. 

For the generic drugs ⁽¹⁰⁾ every investor would want to start getting a return in a reasonably short time e.g. three ⁽¹²⁾ after they file their ANDA ⁽¹⁰⁾ approval application and have an approved plant producing salable products. They do not have unlimited time to invest and expect “maybe return” from an idle plant that will be approved 12 to 48 months after filing the approval paper work, the current scenario. CDER’s ⁽⁶⁾ current processes and methods do not and would not meet their expected time table. They have to be changed. 

 

Since US Government has not been successful in bringing generic manufacturing home, it might be prudent to consider the proposed plan along with a tender process ⁽¹⁴⁾  and/or a Puerto Rico model ⁽¹⁵⁾ to attract investors in setting up ANDA ⁽⁸⁾manufacturing operations in USA.

 

Under the proposed plan simplification of the NDA ⁽¹³⁾ and ANDA ⁽⁸⁾ approval processes, as suggested earlier FDA ⁽¹⁾ would have to reorganize CDER ⁽⁶⁾ as two different operating entities, Generic ⁽⁸⁾ and Brand ⁽¹³⁾. Each drug category will have their own review teams. Discussion here is focused on generic drugs and its experience and time lines could be adopted by the brand ⁽¹³⁾team also. 

 

Why the reorganization of CDER ⁽⁶⁾ is being recommended? Rational is by having separate brand and generic drug approval entities/organizations, each would be held accountable for its approval performance. They will have to be run as “for profit” entities or as manufacturing organizations where their performance is measured by the results of each fiscal year. This suggestion due to accountability criterion would face highest resistance from FDA ⁽¹⁾ and HHS ⁽⁴⁾.  

 

Each group (brand and generic) with in CDER ⁽⁶⁾ will operate similar to a manufacturing organization they will approve applications (call them products) meeting “quality by design” criterion rather than FDA’s and pharma’s current “quality by analysis” ways. FDA ⁽¹⁾ is very familiar with these two terms as it adopted and promoted them early 2000. Each group, ANDA ⁽⁸⁾ & NDA ⁽¹³⁾, has to present to the US population and the US Congress unlike the current method ⁽⁹⁾ how many applications were filed and are approved in each fiscal year (October 1 of the current year to September 30 of the next year). This way any issues related to their performance can be quickly addressed.  

Expectations of ANDA ⁽⁸⁾ approval time, THREE months ⁽¹²⁾, are necessary and critical to every investor as they want to start getting a return on their investment in a reasonable time. No one will invest in US otherwise. Another option each investor has to be given is the opportunity of directly distribute ⁽¹⁶⁾ drugs if they chose to do so. PBMs (pharmacy benefit managers) ⁽¹²⁾ will not like this option. Product quality and consistency has to be paramount ⁽¹²⁾. Investors will have to be tighten their manufacturing processes to assure quality is not compromised ⁽¹²⁾. 

 

For any company to invest in US manufacturing they have to select and decide the product they want to produce. It is suggested that FIVE years ⁽¹⁷⁾ before a patent is to expire, the brand company and US FDA ⁽¹⁾ will make public every detail of the approved drug, dosages, drug performance, purity, solubility, dissolution and stability profile or anything that FDA’s ⁽¹⁾ ANDA ⁽⁸⁾ group considers critical for approval and domestic production ⁽¹⁰⁾. There will be bruhaha about this requirement from within FDA ⁽¹⁾ as the core competencies of its personnel will be tested. Companies holding patents most likely will block the suggested five year requirement. 

 

Sharing brand drug details would prevent the practice of smuggling brand drug samples ⁽¹⁸⁾ to determine their performance and emulate them for the corresponding generic drugs. We have to recognize and demand from FDA ⁽¹⁾ that their sole objective for existence is to assure brand and generic drugs meet the quality and performance. If by providing the details about the drug’s facilitates the commercialization process, takes the guess work out and reduces commercialization time of generics, it is good for the country and humanity. Each drug producing company has the obligation that their product meets the expected standard and performance. Any excursion should be treated as criminal violation and treated such ⁽¹²⁾. US Congress has to decide the penalties.   

 

For all the above to happen FDA’s ⁽¹⁾ ANDA ⁽⁸⁾ Group will have to provide potential investors MOCK filled applications ^{(7,19,20,21,22,23,24)} for every “to be” generic drug which if followed accurately will minimize the filing and approval time. These applications would act as a roadmap that can be followed by anyone who wants to produce any generic drug. These will include everything from raw materials, manufacturing processes, testing methods, bioequivalence, product performance, solubility and any other information FDA ⁽¹⁾ considers is necessary for approval. ANDA ⁽⁸⁾ group should provide the necessary information as if they themselves were filing the paperwork for an approval. Again, the allocated FIVE ⁽¹⁷⁾ years for sharing information about the to expire brand drug will give each investor ample time to develop and commercialize the best and economic manufacturing process and be producing quality drugs from the onset. It is my conjecture that this time will lead to incorporation of better manufacturing technologies ⁽²⁶⁾.  

 

I am sure that the suggested need for ANDA’s ⁽⁸⁾ mock application filing ^{(7,19,20,21,22,23,24)} would raise considerable uproar within FDA ⁽¹⁾, the brand pharma companies and the supporting communities. We have to recognize that without such information the current long approval processes will continue and no one would invest in USA manufacturing facility for the generic drugs. ANDA ⁽⁸⁾ group personnel at CDER ⁽⁶⁾ with their years of experience in reviewing and examining various generic applications should not have any problem preparing mock documents. Their knowledge and experience will be put to test.  

 

Since the mock filled applications will be based on experience of CDER ⁽⁶⁾ personnel any and every question from applicant would have been addressed or can be quickly resolved. It is expected these applications are based on real information needed by FDA every bit of “analysis paralysis” that can happen, will be completely eliminated resulting in faster approvals. Any flaws in the mock applications that lead to filing and approval delays will suggest that the personnel at FDA are not qualified to review such filings. Mock filled applications will help filing of brand drugs also. 

 

Provisions of Hatch-Waxman Act ⁽²⁵⁾ or any other similar act will have to be reviewed, revised and/or updated so that the necessary filing information is available to every potential investor and there are no bottlenecks. 

 

Reorganization of FDA ⁽¹⁾ should not take more than three months. All the above suggested information should be available to potential investors in a short time after reorganization of CDER ⁽⁶⁾. There will be significant resistance to the proposed change. It is possible that the reorganization of CDER ⁽⁶⁾ might require Presidential action with accountable timelines to bring generic pharmaceutical manufacturing home. Reorganization has to be on war footing and the reorganization has to be treated as a remedy to national generic drug supply threat. 

 

If the proposed reorganization or similar effort does not become a reality, nothing will change and no one will invest any money in generic drug production is USA. It is reiterated that FDA ⁽¹⁾, HHS ⁽⁴⁾, and other groups including US Legislators might interfere in the suggested plan. 

 

FDA ⁽¹⁾ or the brand company suggesting the data that is necessary for generic drug filing is proprietary. However it is essential for approval is blocking commercialization of the generic drugs. President or the US Congress may have to re-write the current laws if the brand companies and FDA ⁽¹⁾ interfere or delay the commercialization of generic drugs. 

 

Generic drug producer company has to have the option to sell the drug directly to patients by routes and methods of its choosing. If for some reason any approved generic drug that is on the market fails FDA’s ⁽¹⁾ independent testing and drug efficacy distribution company (pharmacy benefit managers) has to be held accountable ^{(3, 12)}. Overseas companies have drugs on DMF⁽²⁷⁾ list. They might be using this listing to promote their products in other countries. If these companies are not producing for sale in USA they should be delisted if they do not have sustained sales in USA e.g. two years. 

 

What has been proposed above for domestic drug manufacturing pathway needs to be reviewed, thought through and modified to create a landscape that will bring generic drug manufacturing home. If USA does not make an effort nothing will change. 

 

October 3, 2025 FDA proposal ⁽¹⁰⁾ suggests that companies will get a priority review if they did their bioequivalence studies in the United States. Irony is that the testing will be on imported generics. It is ironic that FDA is still not thinking of bringing generic drug manufacturing home. 

 

Again, presented here is an alternate to bring generic manufacturing home that has not been proposed or discussed. May be it is time. I have not dotted every “i” and crossed evert “t”. I ask you the readers to add them as comments to make the  process easier and better. 

 

Girish Malhotra, PE

 

EPCOT International

 

References:

1.     Food and Drug Administration

2.     Federal Register https://www.federalregister.gov

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

4.     Department of Health and Human Services (HHS) https://www.hhs.gov

5.     Phlow Corporation: Trump-era federal Covid Contract recipient has yet to meet major deadlines, July 9, 2022

6.     Center for Drug Evaluation & Research

7.     Profitability through Simplicity

8.     Abbreviated New Drug Application

9.     Generic Drugs Program Activities Report - FY 2024 Monthly Performance Accessed October 30, 2025

10.  ANDA Prioritization Pilot to Support U.S. Generic Drug Manufacturing and Testing, Accessed October 3, 2025

11.  Prioritization of the Review of Original ANDAs, Amendments, and Supplements Accessed October 31, 2025

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

13.  New Drug Applications (NDA)  

14.  Malhotra, Girish: An Outlier Plan to Bring Pharmaceutical Manufacturing to USA in One Year, Profitability through Simplicity, April 28, 2025  

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

16.  Malhotra, Girish: Identifying the Root Causes of Drug Shortages and Finding An Enduring Solution, Profitability through Simplicity, December 7, 2018  

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

18.  Eban, Katherine, Bottle of Lies Harper Collins 2019

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

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

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

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

23.  Malhotra, Girish: Strategies to Increase Generic Drug Competition and Bring Manufacturing to The United States of America, Profitability through Simplicity March 16, 2020 

24.  Malhotra, Girish: Executive Order 14293 & FDA Processes Profitability through Simplicity, August 8, 2025

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

26.  Hatch-Waxman Act

27.  Drug Master Files (DMF) Accessed November 2, 2025

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

 

Let us "THINK DIFFERENTLY'. It is time especially for pharmaceuticals

 This ⁽¹⁾ is an interesting report of spending tax payer (over billion dollars) and company money with no return. Perspective presented is mine and not influenced by any "for or none profit entity". 

 

Goals are noble but the pathway is very prickly and difficult as it has been spun many times in the last 10 plus years with no results. 

 

Companies who need to innovate their processes and technologies do it themselves as we all have been taught the fundamentals of chemistry, chemical engineering and their applications. If we cannot then we have an issue with our teaching and practice methods.

 

FDA's suggestion of advanced manufacturing technologies suggested ELEVEN YEARS ago has gone nowhere. New names have been given to the same dance. 

 

REAL continuous manufacturing has been taught (nonstop) i.e. raw materials in and product out and practiced for over 80 or more years and pharma has avoided considering it. It needs to revisit as creativity and imagination is needed. It has been done successfully in fine/specialty chemicals, older cousin of pharmaceuticals (active ingredients and their formulations. Pharmaceuticals are still stuck at "B" (batch) and to move to the adjoining letter "C" (continuous) totally different landscape and methods are needed. We need to "THINK DIFFERENTLY". 

 

Like other projects "Equip-A-Pharma" will also be a failure. Why? Companies have to have a need for the technologies for their products. No need no project and monies get squandered. Products need different tunes to dance. It cannot be the same tune and different dances. It will go nowhere, my conjecture.

 

HHS comment "Traditional pharmaceutical manufacturing is often too rigid and slow to adapt to changing demands". There is reason as its affiliate FDA has never been on the same page. Again companies have to write their own music and lyrics. 

 

Battelle Memorial Institute and Aprecia; BrightPath Laboratories; Rutgers University; and the Mark Cuban Cost Plus Drug Company have chased and are chasing a dream on someone else's dollar. It is easy to go that route.

 

Lastly artificial intelligence (AI) is the supposedly the answer but its actual ignorance (AI) of reality is an issue and comes in the way.

 

We have the knowledge and desire to excel but if we are going to sing 60 year old music today, not many will listen. Observations are welcome.

 

Girish Malhotra, PE

 

EPCOT International 

 

Reference:

 

Advanced Mfg. in Pharma: Where Does It Play? September 18, 2025

Physical Properties of Chemicals, their Mutual Behavior i.e. SOCIOCHEMICOLOGY and Process Simplification

Linked is an OLD article (April 1, 2012) might be of interest. It is not April Fool's day pun. 

 

“Focus on Physical Properties To Improve Processes https://lnkd.in/ea7nECDN”

 

Social behavior of chemicals coined as "Sociochemicology" https://lnkd.in/eFCFE-Rk capitalized can simplify and innovate chemical manufacturing processes.

 

1.    Process Simplification and The Art of Exploiting Physical Properties, Profitability through Simplicity (https://lnkd.in/eViU6nW) March 10, 2017

2.     Sociochemicology: Redefining Chemical Process Design for Efficiency and Sustainability, Profitability through Simplicity https://lnkd.in/e-PeH5AV, February 26, 2025

 

These might be of interest.

 

Girish Malhotra, PE

 

EPCOT International