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