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 months ⁽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 ^{(7,19,20,21,22,23,24,25)} 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 ⁽²⁵⁾.  

I am sure that the suggested need for ANDA’s ⁽⁸⁾ mock application filing ^{(7,19,20,21,22,23,24,25)} 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

Pharma’s Advanced Manufacturing Technologies: REALITY OR FIGMENT OF IMAGINATION

USFDA at least since 2013 ⁽¹⁾ has been promoting use of advanced manufacturing technologies (AMT) and that includes “continuous manufacturing (CM) ⁽²⁾ for the manufacture and reduce shortages of drugs ^(3,4,5). It has held various conversations and even involved National Institute of Sciences (NAS). This report “Building Resilience into the Nation's Medical Product Supply Chains ⁽⁶⁾ is a disturbing as it suggests increasing reliance through foreign relationships. 

 

FDA ⁽⁷⁾ has continued to convince the pharmaceutical industry to use advanced manufacturing technologies (AMT) but seems like no one is buying what it has been selling.

 

What are these technologies is not clear. Do AMT include manufacture of API along with their formulations or anything else? A clarification from FDA was asked from its CDER/OPPQ/Office of Policy for Pharmaceutical Quality. A very terse response was received “they will respond in several weeks”. This is especially enlightening and interesting when FDA has been touting to the world to adopt such technologies. If FDA is trying to promote adoption of better manufacturing technologies, it would be beneficial if they were more forthcoming in addressing asked questions.  

 

Even after all the conversations and congressional hearings and claims that these will reduce shortages FDA’s effort that has not resulted in any progress in commercializing AMTs at the pharmaceutical companies. This basically suggests that this effort is not going anywhere. If after effort of more than five years and millions of tax payer dollars that have been doled out to universities and other institutions nothing meaningful has happened.  It basically suggests that companies are not buying what USFDA is selling.

 

It is ironic that FDA wants companies to incorporate “continuous manufacturing (CM) ⁽²⁾” but has not shared what is its understanding and definition. In the manufacturing world there is an established definition ⁽²⁾. It would be interesting how FDA’s definition compares with the established definition. It also needs to very clearly explain what does it call “drug manufacturing”. Is it just formulation of active pharmaceutical ingredients (API) or combination of manufacture of APIs and their formulations? We have to remember that without API there is not drug. It is just a placebo. 

 

FDA has called formulation of certain cancer cure drugs (limited global population which means limited demand) as continuous processes (CM) ⁽⁸⁾. Involved companies formulate batch produced API to finished products. Since these products are formulated on stop and go basis i.e. batch production ⁽⁹⁾, the underlying question is why FDA distorting facts and calling these processes CM. Is it trying to convince the pharma industry that it needs to change its manufacturing practices? Justification and rationale are needed. Even press has been talking about CM ⁽²⁾ when they have no idea what it means. 

 

Based on formulation and compaction technologies that have been commercial and are used to produce many products, question that needs to be addressed is “why the pharmaceutical industry has not adopted established (more than fifty years) technology “en masse”. Is it lack of experience, business model or regulatory interference or being comfortable and profitable with quality by “analysis paralysis” processes? 

 

It is a well-known fact that industry invents drug products. New and/or existing technologies and methods are used produce quality products. However, FDA’s telling the industry that new technologies need to be approved ⁽¹⁰⁾ before they can be implemented is a deterrent for brand and generic drug industry. No one knows what these technologies are. businesses. With FDA’s staff having minimal to no or minimal experience in product and process development, design and commercializing any drug molecule and their manufacturing processes, it would amount to further delays from the current times in brand and generic products. This is an un-necessary interference and oversight of a company. Question is how FDA will help. 

  

Industry should be meeting the necessary drug performance criterion using the methods and processes it has developed, tested inhouse and would want to commercialize ASAP. Every product goes through three steps a) lab, b) pilot plant and c) commercial scale. This will be true for every product if it will be produced using a continuous process ⁽²⁾. Due to FDA staff’s limited experience suggested pre-approval review etc.⁽⁷⁾ will result is further commercialization delays as they have no hands on experience of process development. This will result in further commercialization delays. If the industry does not see value in this effort they will not change their  existing practices and/or consider any new technologies. 

 

USFDA has to be very clear of the pathway it wants industry to follow to implement new technologies. FDA has to layout parameters/questions regarding the technology it wants to the industry to address along with a timetable. Goal has to be commercialization of drug in minimal time after its efficacy has been recognized by the pharma company and proven. Pathway for brand and generic drug will be different. There is big gap between FDA and industry as no headway has been made to improve manufacturing technologies. Industry has to recognize financial value and they do not see it as they are profitable. 

May be it is time for FDA to consider alternate ways so that the pharma industry’s manufacturing can come to 21^st Century. It has tried to corral and impress US congress using its resources, as discussed earlier, but no one has budged. It is my conjecture that nothing will change unless the pharmaceutical industry (development and manufacturing) gets involved. They would not till they see a return. Alternate presented is my own and not influenced by any “for profit and nonprofit” organization. 

 

Pharmaceutical industry would be enthusiastic and welcoming if products produced using better manufacturing technologies could be commercialized much sooner than the current times for NDA (new drug applications) and ANDA (abbreviated new drug applications). For that to happen the triumvirate (FDA, Pharma companies, and Pharmacy Benefit Managers (PBM)) have to change the current methods. My thoughts are a stretch and will face resistance from each. Most will come from FDA and PBMs. Pharma companies most likely would like them as they will lead to shorter time needed for commercialization i.e. higher revenues and profits.  

 

FDA: 

 

FDA when it comes to NDA and ANDA approval needs to eliminate every pre-approval meetings and that includes any new manufacturing technology introduction and use templates to get information it would consider necessary for their review and approval ^(11,12). These meetings are suggestive that the applicant companies do not know and/or understand what all is necessary for approval and they have to teach FDA what is the rationale and value of their innovations. Once FDA has the knowledge, it is possible that approval times could be reduced from current times ^{(13, 14, 15)}.

 

Is FDA personnel due to lack of their experience in process development, scaleup and commercialization especially in “continuous” API and formulations using these meetings to further delay approvals. Basically this could be considered that FDA is learning on the fly what all is necessary for approval. FDA needs to create its expectation guidelines for every new (NDA) and existing (ANDA) drug each applicant company has to follow. These guidelines would be routinely updated so going forward companies. Assimilation of this suggestion will be difficult for FDA. 

 

Pharma companies: 

 

Pharma companies have to have every “t” crossed and “i” dotted when it is submitting information required by FDA for their NDA and ANDA as if they will consume first tablet that comes of the production line and their life depended on it. For continuous API manufacturing and their formulations it is very likely that pharma’s current manufacturing landscape would have to be changed ^{(16, 17, 18)}. Companies would be challenged by FDA as they might have to familiarize FDA personnel with nuances of continuous manufacturing. Not having any process development, scale up and commercialization experience this can be a challenge. Chemists and chemical engineers will need company support, a challenge.  

 

PBMs:

 

For Pharma companies to get excited about consideration and incorporation of newer and better manufacturing technologies, in addition to faster approval than current times, they should be allowed to direct market their FDA approved products by bypassing the formulary lists. Patient and physician should be deciding which approved drug they want to use. PBMs should not be interfering in patient’s life. Having a choice of drug would bring highest quality product at the best price competition to market. Competition is healthy and good for encouraged. PBMs are not required to meet quality standards. They should be held accountable ⁽¹⁴⁾.

 

Yes in the final analysis suggestions made here could be considered radical and not to the linking of parties involved. FDA has been going around with all sorts of permutations and combinations but nothing meaningful has materialized. It has not created an environment to innovate. Pharma industry has ignored FDA’s suggestions. PBMs have no interest in reducing shortages. Unless the accountability is shared by each party involved, US drug system (manufacturing, approval and distribution) have and will limp along and patient will continue to suffer. 

 

Path forward:

 

With FDA’s effort of more than eight years, no progress has been made to incorporate proven better manufacturing technologies used elsewhere in API manufacture and their formulations. Pharma manufacturers are comfortable with the current methods that have been in use from 1940-‘50s as they are profitable ⁽¹⁸⁾. PBMs have no interest in what manufacturing methods/technologies are used as they just sell/distribute drugs to patients at their partial monopoly prices. Shortages have become way of life. An outlier approach is needed if we want to reduce shortages and include better manufacturing technologies. 

 

FDA could promote the modified filing process with a stipulation that companies will have faster approvals than the current times i.e. higher profits. As part of the buy in for shorter approval time, FDA could use its legislative clout and bypass the current marketing channels i.e. formulary constraints. Manufacturers would offer the drugs to patients through alternate channels. PBMs will resist these suggestions as their stranglehold on generic markets would be influenced. 

Suggested pathway should encourage generic manufacturers to invest in better manufacturing technologies i.e. continuous API manufacturing and their formulations. If FDA’s test with generics is a success, it could be extended to brand drugs. Yes brand drug product and process information requirements for approval will be different but the current logjam of slow action will be broken. 

 

FDA would need to start the approval simplification process by creating templets that detail information needed for approval. Creation of information asking templets ⁽¹⁴⁾ could be test of FDA’s internal knowledge and competence. There could be significant internal resistance as the review and approval methods would change. FDA’s pre-meetings etc. would have to be curtailed. This would place the onus of convincing FDA to grant the approval. Companies have more to lose if they do not receive timely approval. Such a change is needed if we collectively want to simplify the age old process. To implement the suggested change FDA may have to avail congressional help, if necessary.

 

Companies may include additional information, some of it could be redundant. Excess of submitted information may help the approval process. In the proposed process FDA personnel will still have an opportunity to ask for additional information ⁽¹⁴⁾to complete the review resulting in grant and/or denial. Review and grant process will have defined time window. Once ANDA is approved certain restrictions could be placed on the filing company i.e. it cannot transfer the approved ANDA to any other profit making company in the next twelve months and it has to produce the product for sale in USA within 1-4 months of the approval. Success with generics could be applied for brand drugs.

 

Since companies will have FDA decision in a finite time rather than unknown time, they should be enthusiastic about the suggested process. They would be able to commercialize their manufacturing process innovations and get a better return on their investment. Yes in the final analysis suggestions made here are radical and may not to the liking of some  involved. 

 

FDA and US Congress have been talking and making noise but no solution has been proposed. As suggested earlier chemical engineers are not practicing unit processes ⁽¹⁹⁾ and unit operations ⁽²⁰⁾ they have been taught to the fullest extent. The process outlined ^{(16, 17,18)} will allow them to incorporate them and create excellent processes to produce quality products. It is time pharma manufacturing comes of age. 

 

Product and manufacturing process technology innovation comes from pharma companies. They do their first part but as said earlier dur to profitability they have lagged on the second part. Unless responsibility to reduce shortages is shared by each party involved, US drug system (manufacturing, approval and distribution) will continue to limp along and patient will suffer. It is time to consider better alternate processes to reduce shortages that include better manufacturing technologies and alternate drug distribution model. We have the minds and chutzpah to excel. Time is now.  

 

Girish Malhotra, PE

 

EPCOT International 

 

References:

1.     Strategic Plan for Preventing and Mitigating Drug Shortages  Accessed March 31, 2024 

2.     Continuous Production

3.     TESTIMONY OF JANET WOODCOCK, MD December 10, 2019

4.     Agency Drug Shortages Task Force October 30, 2019 https://www.fda.gov/drugs/drug-shortages/agency-drug-shortages-task-force

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

6.     Building resilience into the Nation’s Medical Product’s Supply, National Academy of Scienceshttps://nap.nationalacademies.org/read/26420 Accessed April 22, 2022

7.   Advanced Manufacturing Technologies Designation Program, Guidance for Industry, December 2023 https://www.fda.gov/media/174651/download   

8.     Malhotra, Girish: Batch, Continuous or "Fake/False" Continuous Processes in Pharmaceutical Manufacturing,Profitability through Simplicity, July 20, 2017

9.     Batch Production https://en.wikipedia.org/wiki/Batch_production

10.  Lifecycle of an Emerging Technology Program (ETP) https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/lifecycle-emerging-technology-program-etp

11.  Malhotra, Girish: Can the Review and Approval Process for ANDA at USFDA be Reduced from Ten Months to Three Months? Profitability through Simplicity, March 25, 2017

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

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

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

15.  Malhotra, Girish: Roadmap to Reduce Drug Shortages Profitability through Simplicity October 30, 2023

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

17.  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

18.  Malhotra, Girish:  Active Pharmaceutical Ingredient Manufacturing: Nondestructive Creation DeGruyter April 2022

19.  Shreve, R. Norris: Unit Process In Chemical Processing, Ind. Eng. Chem., 1954, 46 (4), pp. 672–672

20.  Unit Operation, https://en.wikipedia.org/wiki/Unit_operation , Accessed July 11, 2017