Bring Pharmaceutical Manufacturing Back to USA: Additional Thoughts and Recap

This blog post recaps some of the ideas that have been proposed in the recent past and also presents some additional ideas to bring pharmaceutical manufacturing to USA. Task at hand is a challenge as many vested and personal interests that can be a major hurdle to produce active pharmaceutical ingredients (API) and their formulations in the United States of America ⁽¹⁾. Perspective presented in my own and devoid of any financial relationship with any profit or non-profit making entity. 

Recap:

Every profit making company will manufacture their products in the country where they can maximize their profits. In the last twenty five years US API producers and their formulators could not compete with imports from overseas as the US based manufacturing companies could not give the pharmacy benefit managers and insurance companies the levels of profits overseas companies could give. In addition, companies instead of innovating manufacturing technologies to deal with challenges posed by the environmental laws to preserve the eco systems opted to partner with companies that had to deal with less stringent environmental laws. These could have allowed them to capture the ever growing global markets ⁽²⁾. Consumers (patients) in the developed countries became dependent and addicted to the lower generic drug prices passed on by the companies that came from not proving bioequivalence and much less stringent environmental compliance laws. 

New considerations to bring generic pharmaceutical manufacturing: 

Ators mentioned in earlier post ⁽¹⁾ also need to consider the following if manufacture of pharma has to be brought to the United States. 

1)     Financial Incentives: Any company establishing a pharmaceutical manufacturing plant in the US should be given a TEN year tax benefit. This would be a great incentive to have a pharmaceutical (API and formulation) plant in US. Companies would lie to get this advantage.

2)     Level the playing field: Environmental Laws: Any imports of generics to US have to comply with US environmental laws at producer’s manufacturing sites ^{(3, 4, 5)}.

3)     Eliminate the Formulary lists: If a drug is approved by FDA, it means it is a useful drug for the disease, rather than being selected by PBMs (Pharmacy Benefit Manager) who are in the name of getting the best price benefiting from buying and selling.

4)     Direct Marketing to Patients: Let the pharma manufacturing companies do direct selling to patients through approved channels ^{(6, 7)}. This will bring in competition and quality, a normal expectation, through use of best technologies which has eluded pharmaceutical manufacturing. 

Recent Blog Posts:

1)     Product Quality: Any company and that includes every PBM or their agent or direct/indirect importer of generic drugs in the supply chain product quality non-conformance has to held accountable through ban of sale of such products in the US. If the product does not meet the established quality as approved by US FDA and agreed by the ANDA filing company its approval should be withdrawn ^{(1, 8, 9)}. No 483 should be issued.

2)     ANDA Approvals: Any company wanting to produce generics in US should have their ANDA review and approval done in THIRTY DAYS ^{(1, 9)}. This will be a task as US FDA will have to change its modus operandi. If FDA cannot accomplish this approval timetable and stay with the current model, there is no incentive to invest in manufacturing USA.  

It should be our expectation that our legislators and regulators (ators), who claim to be really serious about continued supply of drugs and healthcare (PPE, personal protective equipment included), will find pathways to accomplish and serve the strategic needs of the United States of America unless they are influenced by vested interests. Pharmaceutical companies will have to be proactive and compete for the market and profits. PBMs will be an interference as their profit landscape could change if direct prescription sales come to fruition. Regulators could find their influence curtailed. 

Creativity and imagination would be needed if US wants to bring pharmaceutical manufacturing home e.g. in the next 365 days. 

Girish Malhotra, PE

EPCOT International

1)     Malhotra, Girish: Euphoria to Bring Pharma Manufacturing Home to United States its Reality and Challenges, Profitability through Simplicity, May 23, 2020

2)     Malhotra, Girish: An Alternate Look at the Pharmaceutical World Revenues and Drug Affordability, Pages 2-5, CPhI Annual Industry Report, 2017

3)     Malhotra, Girish: Can Uniform Safety, Health and Effluent and Manufacturing Standards Create Process Technology Innovation and Competition in Pharmaceuticals? Profitability through Simplicity, January 10, 2017

4)     Malhotra, Girish: Why Have the Fine and Specialty Chemical Sectors Been Moving from the Developed Countries? Profitability through Simplicity, February 9, 2009

5)     Malhotra, Girish: Pharmaceuticals, Their Manufacturing Methods, Ecotoxicology, and Human Life Relationship, Pharmaceutical Processing, November 2007 

6)     Malhotra, Girish: Improving Drug Affordability for the United States Populous through Alternate Business Models, Profitability through Simplicity, May 4, 2018

7)     Malhotra, Girish: Could Amazon (A), Berkshire Hathaway (B) and J.P. Morgan Chase (M) be the Anti-Ballistic Missile (ABM) needed to Control/Curb Rising Healthcare Costs? Profitability through Simplicity, February 9, 2018

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

Strategies to Increase Generic Drug Competition and Bring Manufacturing to The United States of America

US FDA recently finalized “Guidance for Industry on Applications for Drugs with Inadequate Generic Competition” ⁽¹⁾. and it tells us it is the same play with different buntings. This guidance/process is totally inadequate as it is mired in FDA’s current lethargic and controlling practices. It renames the existing ANDA approval process and suggests it will create competition. However, except for minor tweaks and window dressing it is no different from what has been and is the practice.

FDA has a unique opportunity to create a legacy, bring manufacturing jobs home and address national security issue dues to potential drug shortages. It can also at the same time let the companies innovate manufacturing technologies, lower manufacturing costs, improve profits and improve affordability. Unless a process of “nondestructive creation” outlined below is adopted and implemented, the new proposal is a useless exercise of no value. In the outlined proposal there will be challenges but compared to sending man to the moon, the process would be a cake walk. There is no financial relationship with any entity. 

Following proposal/road map will not only create generic competition but also assure continued strategic drug supplies to the residents of United States. Under this scenario FDA has to grant or deny ANDA applications in 90 DAYS from the date of filing if they are properly filled and submitted ^(2,3). For this to come to fruition FDA has to create ANDA a simple filing process and environment. FDA would use the current fee structures for ANDA application filings and approvals. 

For 90 day approvals to happen FDA has to tell the industry the exact information it needs so that the ANDA can be granted or denied in the allocated time. Application will be equivalent “process operating instructions” given to any applicant filing ANDA and if followed as designed, will result perfect application (quality product) that will be approved 90 days or less. With any filing applicant guarantees that is will produce quality products.

Such filing process will be equivalent to FDA writing operating instructions that any operator (company) can follow to create a perfect product (ANDA application). I equate this exercise to be QUALITY BY DESIGN operating instructions. If any applicant company decides to produce the API or formulate in the United States 

US Government should give companies preferential ANDA approval time of 30 days vs. the proposed 90 days which includes inspection if they manufacture drugs in the United States. US has used such preferential treatments in the past ⁽⁴⁾.  

Regulators and companies cannot have any meetings prior to filings to address/answer any questions. Once the application is filed no new additional information except for minor clarifications can be asked by the regulators. 

Companies participating in this process have make sure that they will produce the quality product that has been approved by US FDA and follow FDA cGMP requirements on continued basis. If on random testing or inspection their products in US market does not meet quality specifications which they had committed to in their granted application, NO 483s will be issued and their production shut down for the next TWO years.

FDA’s filing instructions (operating instructions) that would be detailed but general enough to apply to every API and formulations application ^(5,6) . It will necessitate that FDA personnel preparing such instructions have complete understanding of API and formulation processes. Once such instructions are prepared they will have to be internally tested by FDA reviewers to make the application perfect.  This would be equivalent to operators at a manufacturing site testing the operations instructions to see if they are able to produce expected quality product. If not, the processes would need to be repeated till they produce perfect quality product.

Following time table would be followed for ANDA submissions and their grant/denial. 

Plant in USA		Plant outside USA
Day 1	Application arrives at FDA	Day 1	Application arrives at FDA
Day 7 from the filing date	FDA informs the applicant company for completeness or asks for missing information or clarifications. If no additional information is needed the review process continues.	Day 15 from the filing date	FDA informs the applicant company for completeness or asks for missing information or clarifications. If no additional information is needed the review process continues.
Day 15 from the filing date	Company submits the needed information. Review process continues. Plant inspection is scheduled.	Day 45 from the filing date	Company submits the information. Review process continues. Plant inspection is scheduled.
Day 30	Company is granted or denied the ANDA application	Day 90	Company is granted or denied the ANDA application

Girish Malhotra, PE

President

EPCOT International

1.     Competitive Generic Therapies Guidance for Industry , March 14, 2020 

2.     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 Accessed March 15, 2020

3.     Malhotra, Girish: What Is Needed for a Regulatory Approval of NDA/ANDA Filings in 90 Days? Profitability through Simplicity,October 24, 2018 Accessed March 15, 2020

4.     Coronavirus shows US needs to restore pharmaceutical production — in Puerto Rico, New York Post, March 7, 2020 Accessed March 16, 2020 

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

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