All opinions are my own.

Saturday, May 23, 2020

Euphoria to Bring Pharma Manufacturing Home to United States its Reality and Challenges

With COVID-19 amongst us suddenly every “ator” (legislator, regulator, litigator, educator, political operator, news investigator, did I miss any other) has become a policy wonk and has proposals to bring pharmaceutical manufacturing home. It is interesting that many of these “ators” have never designed, developed or seen a manufacturing plant let alone a pharmaceutical plant (1,2, 3). Some have noble thoughts but it is not like waving a wand or twitching a nose and plant making desired active pharmaceutical ingredients (API) and their formulations will appear. Some of the “ators” at regulatory bodies (4) and educational institutions (too many to name) are even talking about advanced manufacturing technologies which they know nothing about as they have never developed, designed, commercialized such technologies at profit making enterprises. We need to be skeptical and take all of the euphoria with grain of salt and tread through the maze carefully as the task at hand is not that easy as it sounds. I am presenting my perspective and have no financial relationship with any ators or any other nonprofit and/ profit making entity. 

Since WTO (World Trade Organization) agreement US has increasingly relied on outsourced medicines. If just thinking that a manufacturing plant will appear overnight and make USA self-sufficient in pharmaceuticals then we all are living in an unreal and a make belief world. Suddenly COVID-19 brought a rude awakening home that US cannot supply its populous many of the generic drugs and faces strategic and national security threat (5, 6) and suddenly every policy wonk (ator) as stated earlier has a proposal to remedy the situation overnight. 

Unfortunately, it is not easy to accomplish task at hand overnight and even in one year. In order to accomplish success many stars have to align and many established and stodgy policies will have to change. Many are the mainstay of FDA’s day to day working. Skeptics, procrastinators, Monday morning quarterbacks, would not be needed. Mover and shakers and can doers would be extremely useful. Lots of fiefdoms and kingdoms will have to accept change. 

In order to bring pharma manufacturing home FDA would have to re-write its ANDA review and approval policies. First and foremost being it has to create processes to get ANDA approval in 30 days if a company establishes a manufacturing plant to produce quality drugs in USA (7,8, 9, 10, 11). FDA is going to resist change as it will loose its stranglehold on pharma companies. However, it can still hold pharma companies accountable for by shutting them down if they cannot produce quality at first inspection or random sampling of their product from the market place (6)

In addition to FDA changing its approval procedures, many other things have to happen and done by the pharma manufacturing companies. They have to create processes that can be fitted in any existing plants in the United States. It will be challenging task. Fitting a square plug in a round hole is not a simple as it sounds (12, 13, 14, 15). Significant effort would be needed to fit the processes in existing equipment. Even with availability of plants engineers will have to figure out and prove that their process modification and innovations would deliver quality products. We don’t have time for grass root plants. 

Since pharma product is a two-step process, API manufacture and their formulations, it is an excellent opportunity to develop realcontinuous formulation operations. Equipment technologies have existed for over 60 years but my conjecture is that most equipment vendors have stood in the way of such formulation processes. This is more due to fear of engineers at pharma companies not having experience, creativity and imagination to design, develop and commercialize excellent processes that will deliver quality product (16). Vendors need not hold hands of clients. This not any accusation but a reality. API except for few products do not have the product volume to be produced under established continuous process definition (17)

Existence of FDA is a must. It should set policies and expectations. Let the companies deliver what it expects rather than telling how and what. FDA has to let the companies innovate rather than telling them what is good for them. If the companies don’t know that then they should not be in the manufacturing business. Engineers excel in what they develop, design and commercialize. Babysitting of companies has to stop. If companies don’t live up the expected minimum after one iteration, they should not be given 483 citation but shut down. 483 have become a medal of honor (18) for the companies. PBMs (pharmaceutical benefit managers) will have to restrained as their profits are going to be impacted. If not restrained, US population will see drug prices go up. 

If US can send the man to the moon and bring him back, bringing pharma manufacturing home is lot easier. If companies get started to bring manufacturing to the United States today, it will take time, effort, creativity and imagination to deliver. We have to acknowledge that US does not have sustained availability of raw materials to produce the necessary drugs. There is lot needed than just saying let’s bring pharma manufacturing home. It won’t happen in a blink. US needs lot of luck. 

Girish Malhotra, PE

EPCOT International 
  1. Rosebush, Lee, Outsourcing U.S. Drug Manufacturing to China was a Mistake—A Lethal One | Opinion, Newsweek, May 5, 2020, Accessed May 22, 2020
  2. Gibson, Rosemary, China Rx: Exposing the Risks of America’s Dependence on China for Medicine, U.S.-China Economic and Security Review Commission, July 31, 2019, Accessed May 22, 2020
  3. A Blueprint  For Enhancing the Security U.S. Pharmaceutical Supply Chain, April 2020, Accessed May 22, 2020
  5. Malhotra, Girish: Health and National Security Issues for the USA and Is The United States of America Prepared, Profitability through Simplicity, May 8, 2020 
  6. Malhotra, Girish: Strategies to Increase Generic Drug Competition and Bring Manufacturing to The United States of America, Profitability through Simplicity, March 16, 2020 
  7. Malhotra, Girish: Long Term Drug Quality Supplies for US, FDA and A New Reality, Profitability through Simplicity, April 3, 2020
  8. Malhotra, Girish: ONE PAGE Road Map to Reduce Drug Shortages, Assure Quality and Improve Affordability, Profitability through Simplicity, December 6, 2019
  9. Malhotra, Girish: Impact of Regulations, Drug Manufacturing and Pharma Supply Chain (PBMs and allies) in Drug Shortages and Affordability Part 1, Profitability through Simplicity, March 8, 2019 
  10. Malhotra, Girish, Impact of Regulations, Manufacturing and Pharmaceutical Supply Chain (PBMs) on Drug Shortages and Affordability Part 2, Profitability through Simplicity, April 3, 2019
  11. Malhotra, Girish: What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days?, Profitability through Simplicity, October 24, 2018
  12. Malhotra, Girish: Square Plug In A Round Hole: Does This Scenario Exist in Pharmaceuticals?, Profitability through Simplicity, August 17, 2010
  13. Malhotra, Girish: Why Fitting a Square Plug in a Round hole is Profitable for Pharma and Most Likely Will Stay?, Profitability through Simplicity, August 1, 2014
  14. Malhotra, Girish: A Radical Approach to Fine/Specialty API Manufacturing, Profitability through Simplicity, January 20, 2010
  15. Malhotra, Girish: The Good, The Bad, The Ugly (1) Complexities of Pharmaceutical Manufacturing, Profitability through Simplicity, April 8, 2018
  16. Vanhoorne, V, Vervaet, C: Recent progress in continuous manufacturing of oral solid dosage forms, International Journal of Pharmaceutics, April 15, 2020, Accessed May 20, 2020
  17. Continuous Production,  Wikipedia
  18. Malhotra, Girish: Are US FDA 483 Citations a "Medal of Honor" or “Rite of Passage” to Disgrace for the Pharma companies? Profitability through Simplicity, October 16, 2019

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