Disclaimer

All opinions are my own.

Tuesday, October 7, 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 have 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

 

Tuesday, September 23, 2025

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

Monday, September 8, 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 

Friday, August 8, 2025

Executive Order 14293 & FDA Processes

US FDA posted a press release “FDA Announces New FDA PreCheck Program to Boost U.S. Drug Manufacturing” (1) outlining its NEW PROGRAM to strengthen its processes. It proposes a PreCheck in response to EO14293 (2)

FDA (1) has suggested TWO steps and they are: 

1.     First, the Facility Readiness Phase provides manufacturers with more frequent FDA communication at critical development stages, including facility design, construction, and pre-production. This phase also encourages companies to provide a comprehensive facility-specific information through a Type V Drug Master File (DMF), such as site operations layout and description, Pharmaceutical Quality System elements, and Quality Management Maturity practices. This facility-specific DMF can be incorporated by reference into a drug application as appropriate. 

2.     Second, the Application Submission Phase centers on streamlining development of the Chemistry, Manufacturing, and Controls section of the application  through pre-application meetings and early feedback.

I am presenting my understanding of FDA’s PreCheck Program processes. I have no financial relationship with any for profit and/or nonprofit organization. 

 

FDA personnel, my conjecture, will never have complete understanding and/or command of each product and process as that is the jurisdiction of the company producing the products. Companies know their manufacturing processes better than anyone else. If they do not then every chemical and pharmaceutical company has a major problem. FDA through this (1) is suggesting they know more about company’s processes, products and manufacturing. As a regulatory body FDA or for that matter EPA also has to rely on what the company is presenting and saying will do to produce quality product/s. Is FDA suggesting that companies do not understand their product, process and manufacturing processes? With that being the case how FDA personnel, that has minimal and/or no experience in process development, manufacturing and commercialization will be able to advise a company of “facility phase readiness”. FDA just put a CART BEFORE THE HORSE and exposed itself for telling the world that best of the chemical/pharmaceutical companies don’t know much about what they commercialize.   

 

It is my understanding that currently FDA and companies meet to address any questions through in-person meetings. In PreCheck what will be different from the current situation. I would be tempted to call this a case of “sanctioned delays”. 

 

Meeting product’s established quality specification, performance and following cGMP guidelines is company’s responsibility and should be demanded by FDA from every company to produce their products. FDA and or any other regulatory body should have the authority to stop production (3) if they do not deliver expected product quality. FDA should very clearly define the information that each company needs to submit for approval. What FDA has issued is complex and needs simplification. My best postulation is even FDA personnel cannot fill an application. USA needs to adopt and consider processes where NDA(new drug application)/ANDA (abbreviated new drug application) (3,4,5) can be approved in 90 days. They have been discussed since 2017 and for EO 14293 to be a success their adoption and implementation is critical (3,4,5).  

 

I posted my first reaction about FDA’s PreCheck on LinkedIn (6) when I saw the news release (1). I consider this as an official sanction for the delays. EO 14293 (2) will never come true as there is no timetable to be met. Without any timetable for domestic production for critical drugs, FDA’s processes (1) are of no value to US population. 

 

We have to recognize that it is company’s responsibility to produce quality drugs and FDA’s responsibility to expedite the approval process. Fact that the Presidents of The United States have issued Executive Orders (2,7,8,9) for the expeditious manufacture of critical drugs and it seems no one has taken responsibility for their implementation. It seems they (7,8,9) have been ignored and gone by the wayside. How FDA’s PreCheck, a new name for existing practice will promote domestic production?   

 

FDA’s processes need revamp. If not done the issue of critical drugs and shortages will keep rearing its UGLY head every so often. There are many vested interests that will interfere (10) in the process and need to stay out the way.  

 

Girish Malhotra, PE

 

EPCOT International 

 

References:

 

1.    FDA Announces New FDA PreCheck Program to Boost U.S. Drug Manufacturing August 7, 2025

2.     EO14293  Regulatory Relief To Promote Domestic Production of Critical Medicines, May 5, 2025

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

4.     Malhotra, Girish: What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days? Profitability through Simplicity, October 24, 2018

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

6.     LinkedIn August 7, 2025

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

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

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

10.  Malhotra, Girish: Most Favored Nation Pricing & Bringing Pharmaceutical Manufacturing Home, Profitability through Simplicity, July 13, 2025

  

Sunday, July 13, 2025

Most Favored Nation Pricing & Bringing Pharmaceutical Manufacturing Home:

Discussion of high drug prices, shortages and brining pharma manufacturing home has been an ongoing subject and it is discussed in every Congress. Executive orders (too many to cite) have been issued and nothing has changed. Interference besides pharmaceutical companies comes from TORS. Who are TORS? They are Distributors, Regulators, Legislators and Litigators. Each has financial interest and do what they can do to derail any and every progress. 

 

Current administration has issued Executive Orders (1,2,3) and we will have to see if anything happens as there are many vested interests in their way to prevent their implementation. Perspective presented is unbiased and not influenced by an for profit and non-profit organization. 

 

To get to Most-Favored-Nation pricing and bring pharma manufacturing home, the current business model along with how pharmaceuticals are distributed in the United States will have to change. All of these are going to be a challenge. Companies with about 2.5 TRILLION dollar revenue (pharmaceutical benefit managers (distribuTORS), pharmaceutical companies, health insurance etc.) will exert every bit use of political influence on (legislaTORS), litigaTORs and RegulaTORS. Reason is very simple. Too much distribution disruption and relearning pharma’s development and manufacturing capabilities can be avoided by money if status quo can bought. However, if the current US administration forces the issue, things will have to change staring from pharma’s methods (product development, manufacturing) and regulatory approval methods. Distribution will be disrupted. Alternate approval methods will have to considered and implemented (4) 

 

For the last twenty years I have discussed manufacturing technology issues and published solutions in articles, my blog and books. Manufacturing processes of the Active Pharmaceutical Ingredient (API) and their formulations are bench top processes. I call them round bottom flask and mortar and pestle processes. They could be easily fitted in the equipment of the age and have been the main stay of pharma manufacturing.

Most of the chemical synthesis manufacturing processes and methodologies are batch processes fitted in the existing equipment. Reasons and rational are simple. Minimize investment. There are other ways improve manufacturing process that also minimize investment, discussed in the books. cGMP practices have to followed irrespective of the equipment used. Involvement of the VILLAGE from inception of the product can simplify the manufacturing processes i.e. lower cost. I am not going into the reasons and rationale but internal complacency, tradition and regulatory needs have been an impediment in use of better processing methods (5,6,7).  Process of continuous improvement does not exist in pharma manufacturing as each modification has to be approved by the regulators, a very expensive process. Result is companies are afraid to make even minor tweaks to the processes. 

 

To bring pharma manufacturing home and companies to profit their practices have to become current. Very creative and imaginative chemical engineers and chemists at the pharmaceutical companies with the cooperation of FDA can BRING PHARMA MANUFACTURING HOME. No such attempt has been made. Billions are being invested in antiquated methods and manufacturing technologies (too many to cite). These will not deliver what is expected by the current US administration.  

 

If any headway has been made at least it is not obvious. I am not sure about recent announcements for new plants that will come on stream in few years should be a consideration of bringing manufacturing home. This is a harsh observation but is a reality. Question is what do they do for US’s short term needs. It seems more of a public relation ploy in front of legislators and press. 

 

In order to bring manufacturing home, pharmaceutical companies have to proactive and be directed by a Pharma Czar (8) who directly reports to the President of the United States. Drug distribution methods and policies will need to be modified. Again undue influence of TORS will have to be warded off.  

 

Fitting processes not only has not only been less productive but also results in high emissions per kilo of the drug. Yes it minimizes investment but there are alternates. They can lower manufacturing costs and they need to be considered (4,5,6,9). Involvement of village would be necessary as after the fact ways that have been practiced have to go by the wayside. 

 

I have presented my perspective in the following and good, experienced chemists, chemical engineers and  business folks need to review. They can practice and/or modify to bring manufacturing home and lower drug prices. Following have been presented to bringing pharma manufacturing home and ways to improve profits. 

 

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

2.     Malhotra, Girish: Health and National Security Issues for the USA and Is The United States of America Prepared May 8 , 2020

3.     Malhotra, Girish: A road map for driving pharmaceutical manufacturing back to the USA by 2025 October 8, 2020

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

5.     Malhotra, Girish: Roadmap to Reduce Drug Shortages and Bring Pharma Manufacturing Home (US) October 30, 2023

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

7.     Malhotra, Girish: An Outlier Plan to Bring Pharmaceutical Manufacturing to USA in One Year April 28, 2025

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

9.     Malhotra, Girish: An Unconventional Analysis: Can the Wrath of Most Favored Nation Pricing (1) be Avoided by Bringing Pharmaceutical Product & Process Development and Manufacturing Practices to 21st Century? July 8, 2025

 

To accomplish the objectives of MFN pricing (2) the MOST IMPORTANT AND CRITICAL item is that every manufacturing change and practice has to come INTERNALLY FROM THE PHARMACEUTICAL COMPANIES as they have command of their culture, process chemistries, understand their manufacturing landscape and every other detail. There are very many vested interests (regulators, consultants, contract manufacturing organizations) that will vie to meddle in but no one knows the business better than folks at the companies. Over the years many have stepped in with no results. Focus has to be razor sharp. Task is not going to be easy unless it is tried and tested internally nothing will change. Companies have the knowledge and what it will take to bring manufacturing home. With the resident talent and application of chemical engineering fundamentals, creativity and imagination the factory costs can be reduced, profits improved and profits improved (5, 6, 7, 8). We need to exploit them. Change has to come and is overdue. May the FORCE be with you. 

 

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

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

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

7.     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

8.     Malhotra, Girish: Profitability through Simplicity